**PREVIOUSLY NAMED NatCell Thymus by Atrium**
The thymus is one of our major immune system glands. The thymus is responsible for many immune system functions, including the production of T lymphocytes, a type of white blood cell responsible for “cell-mediated immunity.” which is extremely important in the resistance to infection by certain bacteria, yeast (including Candida albicans), fungi, parasites, and viruses (including herpes simplex, Epstein-Barr, and the viruses that cause hepatitis). XtraCell Thymus is composed of small proteins and thymus derived factors. It is designed to help the body resist disease and bacteria as well as other unwanted viruses. This is a whole thymus extract prepared from juvenile bovine thymus, with all factors lower than 50,000 molecular weight and minimally antigenic. It is stored and shipped frozen, and is made without preservatives.

Benefits of XtraCell Thymus:

• Nourishes and supports the thymus gland
• Enhances Lymphocyte Proliferation and Maturation by In-Vitro Assays.
• Helps the Body Resist Parasites, Fungi, Bacteria, Viruses and Yeast
• Protects the Body From Auto-Immune Diseases, Allergies, and Cancer
• Treats Acute and Chronic Hepatitis B Infections
• Restores White Blood Cells in Cancer Patients
• Relieves Allergies, Asthma, Hay Fever, and Food Allergies

Each 1 Bottle of 0.3 fl. Oz (9 ml) contains:

• Porcine Thymus Aqueous Extract 0.3 fl. Oz (9 ml)

Suggested Use:
As a dietary supplement, take 2 bottles of Xtra-Cell Thymus per week for the first 2 weeks and 1 bottle per week thereafter. Follow the instructions included in this box or as directed by your healthcare professional.

Warnings: Do not use if security seal is broken or missing. This product may not be suitable for:

• Pregnant or nursing women
• persons taking immunosuppressive drugs or persons allergic to pork products
• Children under 12 years of age.

These little frozen glandulars have done some miraculous things for me and my family's health. They are the most powerful product I have found for strengthening the Immune System. On three separate occasions, they have allowed me to get completely get rid of serious bronchial infections, a flu, and a cold before they ever got bad. Still have not missed a day of work in 4 years and plan to keep it that way. The cost is high, but worth every dime. I recommend adding in Oregacyn for bronchial and sinus infections. And ImmunoKinoko AHCC is a great additional product for cancer and HIV patients.

Read Customer questions and answers about Immune Support in our FAQ.

Contraindications:
No side effects, adverse reactions, or drug interactions have been reported with the use of thymus preparations.

What source is this product from?
The source of bovine glandulars is Government inspected Canadian beef, which is range-fed, organic and never given hormones or antibiotics.

Immune System
Thymomodulin has also been shown in a double-blind study to improve immune function in cases of exercise-induced immune suppression. In addition, preliminary studies have shown the extract to improve immune function in people with diabetes and in elderly people.8 9 10 11 (Extreme exercise, diabetes, and aging are all associated with suppression of immune function.)

Respiratory Infections
Thymus extracts used as nutritional supplements are most often derived from young calves (bovine). The oral calf thymus extract that has been studied scientifically is specially prepared to concentrate small protein-like molecules (polypeptides). This extract (known as Thymomodulin®) has been shown effective in preventing recurrent upper respiratory tract infections.

The ability of Thymomodulin to improve immune function and reduce the number of recurrent infections has been shown in double-blind studies of children and adults with a history of recurrent respiratory-tract infections.3 4 5 6 7

Cancer and Auto-Immune Diseases
Preliminary studies suggest that Thymomodulin may also be helpful in (1) improving one of the T-cell defects in patients with human immunodeficiency virus infection (HIV—the virus that causes AIDS); (2) treating acute and chronic hepatitis B infections; (3) restoring the number of peripheral white blood cells in cancer patients undergoing chemotherapy or radiation; and (4) relieving allergies, including asthma, hay fever, and food allergies, in children.1 2 The effectiveness of Thymomodulin in these conditions may be the result of improved thymus gland activity, or it may be due to the presence of hormones or other biologically active substances in the extract.

Preliminary studies in patients with acute or chronic hepatitis suggest that supplementation with Thymomodulin may be helpful.12 13 However, additional studies are needed to confirm these findings.

In a preliminary study in patients with early HIV infection, Thymomodulin improved several measures of immune function, including an increase in the number of T-helper cells, one of the goals in the treatment of HIV infection.14 Thymomodulin (given orally or by injection) has been used in cancer patients to counteract the decline in white-blood-cell levels that can result from chemotherapy or radiation.15 16 17 18 19 20 In in vitro studies, Thymomodulin and other thymus extracts have been shown to exert a number of effects on white blood cells (e.g., increasing both the bone marrow production and functional activity of white blood cells).21 22 However, it is not yet known if this effect can be achieved with the use of oral thymus extracts.

Allergies
The oral administration of Thymomodulin has been shown in preliminary and double-blind clinical trials to improve the symptoms and course of hay fever, allergic rhinitis, asthma, eczema, and food allergies (in conjunction with an allergy elimination diet).23 24 25 26 27 28 29 30 Presumably, this clinical improvement results from restoring proper control over immune function.

Diseases of the Heart
Thymomodulin given by injection has also been shown to be helpful in the treatment of diseases of the heart muscle (i.e., idiopathic myocarditis and idiopathic dilated cardiomyopathy).31 32 It is not known whether oral thymus extracts can achieve these same benefits.

NatCell Thymus Extract:
1. Cazzola P, Mazzanti P, Bossi G. In vivo modulating effect of a calf thymus acid lysate on human T lymphocyte subsets and CD4+/CD8+ ratio in the course of different diseases. Curr Ther Res 1987;42:1011–7.
2. Kouttab NM, Prada M, Cazzola P. Thymomodulin: Biological properties and clinical applications. Med Oncol Tumor Pharmacother 1989;6:5–9 [review].
3. Fiocchi A, Borella E, Riva E, et al. A double-blind clinical trial for the evaluation of the therapeutic effectiveness of a calf thymus derivative (Thymomodulin) in children with recurrent respiratory infections. Thymus 1986;8:831–9.
4. Galli L, de Martino M, Azzari C, et al. Preventive effect of thymomodulin in recurrent respiratory infections in children. Pediatr Med Chir 1990;12:229–32.
5. Vettori G, Lazzaro A, Mazzanti P, Cazzola P. Prevention of recurrent respiratory infections in adults. Minerva Med 1987;78:1281–9.
6. Longo F, Lepore L, Agosti E, Panizon F. Evaluation of the effectiveness of thymomodulin in children with recurrent respiratory infections. Pediatr Med Chir 1988;10:603–7.
7. Maiorano V, Chianese R, Fumarulo R, et al. Thymomodulin increases the depressed production of superoxide anion by alveolar macrophages in patients with chronic bronchitis. Int J Tissue React 1989;11:21–5.
8. Garagiola U, Buzzetti M, Cardella E. Immunological patterns during regular intensive training in athletes: quantification and evaluation of a preventive pharmacological approach. J Int Med Res 1995;23:85–95.
9. Wysocki J, Wierusz-Wysocka B, Wykretowicz A, Wysocki H. The influence of thymus extracts on the chemotaxis of polymorphonuclear neutrophils (PMN) from patients with insulin-dependent diabetes mellitus (IDD). Thymus 1992;20:63–7.
10. Calsini P, Mocchegiani E, Fabris N. The pharmacodynamics of thymomodulin in elderly humans. Drugs Exp Clin Res 1985;11:671–4.
11. Braga PC, Dal Sasso M, Maci S, et al. Restoration of polymorphonuclear leukocyte function in elderly subjects by thymomodulin. J Chemother 1994;6:354–9.
12. Galli M, Crocchiolo P, Negri C, et al. Attempt to treat acute type B hepatitis with an orally administered thymic extract (Thymomodulin): preliminary results. Drugs Expt Clin Res 1985;11:665–9.
13. Bortolotti F, Cadrobbi P, Criverllaro C, et al. Effect of an orally administered thymic derivative, Thymodulin, in chronic type B hepatitis in children. Curr Ther Res 1988;43:67–72.
14. Valesini G, Barnaba V, Benvenuto R, et al. A calf thymus lysate improves clinical symptoms and T-cell defects in the early stages of HIV infection: second report. Eur J Cancer Clin Oncol 1987;23:1915–9.
15. Kouttab NM, Prada M, Cazzola P. Thymomodulin: biological properties and clinical applications. Med Oncol Tumor Pharmacother 1989;6:5–9 [review].
16. Kang SD, Lee BH, Yang JH, Lee CY. The effects of calf-thymus extract on recovery of bone marrow function in anticancer chemotherapy. New Med J 1985;28:11–5.
17. Schulof RS. Thymic peptide hormones: basic properties and clinical applications in cancer. Crit Rev in Oncol Hematol 1985;3:309–76 [review].
18. Meneses G, Delgado MA, Perez-Machado A, et al. Thymostimulin increases natural cytotoxic activity in patients with breast cancer. Int J Immunopharmacol 1997;19:187–93.
19. Skotnicki AB. Thymic hormones and lymphokines. Drug Today 1989;25:337–62 [review].
20. Ernst E. Thymus therapy for cancer? A criteria-based, systematic review. Eur J Cancer 1997;33:531–5 [review].
21. Vasilopoulos G, Porwit A, Lauren L, et al. The effect of a calf thymus acid lysate on bone marrow cell growth in vitro. Immunopharmacol Immunotoxicol 1988;10:523–36.
22. Skotnicki AB. Thymic hormones and lymphokines. Drug Today 1989;25:337–62 [review].
23. Cazzola P, Mazzanti P, Bossi G. In vivo modulating effect of a calf thymus acid lysate on human T lymphocyte subsets and CD4+/CD8+ ratio in the course of different diseases. Curr Ther Res 1987;42:1011–7.
24. Kouttab NM, Prada M, Cazzola P. Thymomodulin: biological properties and clinical applications. Med Oncol Tumor Pharmacother 1989;6:5–9 [review].
25. Marzari R, Mazzanti P, Cazzola P, Pirodda E. Perennial allergic rhinitis: prevention of the acute episodes with Thymomodulin. Minerva Med 1987;78:1675–81.
26. Genova R, Guerra A. A thymus extract (thymomodulin) in the prevention of childhood asthma. Pediatr Med Chir 1983;5:395–402.
27. Bagnato A, Brovedani P, Comina P, et al. Long-term treatment with thymomodulin reduces airway hyperresponsiveness to methacholine. Ann Allergy 1989;62:425–8.
28. Fiocchi A, Grasso U, Travaglini P, et al. A double blind clinical trials on the effectiveness of a thymic derivative (Thymomodulin) in the treatment of children with atopic dermatitis. Int J Immunother 1987;3:279–84.
29. Cavagni G, Piscopo E, Rigoli E, et al. Food allergy in children: an attempt to improve the effects of the elimination diet with an immunomodulating agent (thymomodulin). A double-blind clinical trial. Immunopharmacol Immunotoxicol 1989;11:131–42.
30. Genova R, Guerra A. Thymomodulin in management of food allergy in children. Int J Tissue React 1986;8:239–42.
31. Miric M, Vasiljevic J, Bojic M, et al. Long-term follow up of patients with dilated heart muscle disease treated with human leucocytic interferon alpha or thymic hormones initial results. Heart 1996;75:596–601.
32. Miric M, Miskovic A, Brkic S, et al. Long-term follow-up of patients with myocarditis and idiopathic dilated cardiomyopathy after immunomodulatory therapy. Immunol Med Microbiol 1994;10:65–74.


THYMUS EXTRACTS:
An International Literature Review of Clinical Studies*
© 1999 Foundation for Immunology and Nutrition, Development, Education and Research
Reviewed by James L. Wilson, Ph.D.

The past 20 years have witnessed an explosive investigation of the immune system and the agents governing it. One area of research involved the use of thymus extracts. These extracts have proven surprisingly useful in a wide variety of conditions, sometimes being the only effective treatment (Skotnicki 89, Kouttab 89, Hadden 89).

OVERVIEW
A brief explanation of cellular and humoral immunity

Although immunity involves every organ and system of the body, the typical conceptualization of the immune system consists of lymphocytes divided into two major divisions: the humoral and cellular aspects. Humoral immunity includes primarily B lymphocytes and has to do with antigen/antibody reactions. These are the reactions involved in type I (immediate hypersensitivity, IgE response, anaphylaxis), type II (hemolytic disease of the newborn, also known as erthyroblastosis fetalis) and type III (Arthrus) hypersensitivities. In antigen/antibody reactions, B lymphocytes secrete antibodies to an antigen. An antigen is any substance, typically a protein, that the body recognizes as "non-self". The antibodies attack an antigen by clumping around it. Simultaneously they weaken it and signal for other aspects of the immune system (especially the complement system and phagocytosis) to immobilize and dispose of the antigen. No direct contact of the B lymphocyte with the antigen is necessary. Cellular immunity, however, is medicated primarily by the T lymphocytes and involves cell to cell contact with microorganisms and other pathogens. The T helpers, T suppressors, T cytotoxic, killer (K) cells and natural killer (NK) cells are part of this system. Macrophages and monocytes are also recruited by members of this array of cells and are involved in constant direct combat with the pathogens and renegade cells that constitute most of the chronic diseases from which we suffer. The cellular branch of immunity is, therefore, responsible for vigilance against neoplastic and aging cells, as well as viruses, fungi (Odds 94), and some bacterial (Berkow 87, p260) and parasitic infections (Rothbard 90, Gasbarre 82).

Maturation of T lymphocytes
Histologically, T lymphocytes mature in the thymus gland but are a part of the myelopoietic cell line and have their origin in the bone marrow. As they develop, they carry specific cell surface markers on the periphery of each cell which are used to identify each cell type. These cell markers change as the cell matures. Immature thymocytes in bone marrow carry a CD1 (also known as T1) marker. Some of them migrate to the thymus gland for maturation beginning in the late part of gestation. The rest continue to migrate to the thymus throughout life with the greatest migration taking place in the first two years of life and at 13-16 years of age. As they mature and begin to migrate out of the bone marrow, thymocytes drop the CD1 marker and begin carrying a CD3 lymphocyte cell surface marker. When a CD3 (also known as T3) cell I brought into contact with an antigen appropriate for a cellular immune response, the T cell matures by committing to that particular antigen and becomes a T helper/inducer cell and hence adds a CD4 (also known as T4) marker to its cell surface. Other T cells become suppressor or cytotoxic cells which carry CD8 (also known as T8) markers. Once T cells are committed, they remain vigilant and committed to that antigen for life but depend upon the presence of the thymic hormones for normal activity (Berkow 87, p260-1).

Thymic hormones and their down stream cell products (such as interleukins and interferons) control all phases of maturation, development, antigen commitment, proliferation and cytotoxic activity of the various T cells. Thymic hormones also stimulate non-specific phagocytic and cytotoxic cells to respond against foreign or "non-self" antigens.

Causes of compromised immune function
It is hard to exist and not pose some insult to the immune system. Indeed, it is the combination of what the body is exposed to and its ability to respond that comprises the adequacy of the immune response. In any epidemic, only a portion of those exposed become infected, only a portion of the infected become ill, and only a portion of those who become ill are overcome and die. The difference in each of these stages is the adequacy of the response of the immune system. There are many factors which have been shown to affect immunity. Nutrient status has been shown to be fundamental to a proper immune response (Berkow 92, p317). Inadequate nutrient intake results specifically in T cell immunodeficiency (Nezu 94, Wing 88); affects delayed-type hypersensitivity (DTH) skin tests; and reduces T cell numbers, proliferative responses to mitogens, and cytotoxic activity (Berkow 92, p318). In addition to overall nutritional status and sub optimal nutritional intake, the following conditions also lend the body to immunocompromised states: excess or lack of exercise (Wiik 96, Boyum 96); physical trauma (Wichmann 98), especially involving head injuries (Sacks 95, Meert 95, Quattrocchi 92) and burns (Cairns 94); inadequate amounts and quality of sleep (Born 97, Wiik 96, Boyum 96, Irwin 96); excess fatigue (Bennet 98); starvation (Nezu 94, Wing 88); smoking (McAllister 98); excessive intake of alcohol (Faunce 97); most recreational drugs including barbiturates (Nagylucskay 92), cocaine (Stanulus 97, Watson 83, Di Francesco 90), marijuana (Cabral 98, Klein 98, Tang 92, Spector 90); and prescription drugs such as steroids (Daynes 95, Berge 94) and narcotics (DeWaal 98, Roy 96, Caar 95, Rouveix 92, Novick 91); iatrogenically induced stresses such as chemotherapy (Periti 87, Rosenthal 87, Rosenthal 88, ten Berge 94), surgery (Samanci 98, Brivio 98, Zaporozhchenko98), radiation (Lieber 98, Tisch 98, Krutmann 98) and some antibiotics (Fietta 83, High 92, Berge 94); extremes of weather (Komarov 85, Stott 76, Kohnlein 73); aging (Hadden 89, Weksler 81); and chronic disease (Fiocchi 86, Cazzola 87, Tas 90). None of the clinical trials reviewed in the following text have attempted to control for more than one of these variables. These additional factors affecting overall immune status will critically influence the effectiveness of specific immunotherapy in restoring an adequate immune response.

Thymus Extracts
Composition of thymus extracts

There has been some confusion concerning the composition of thymus extracts. In part this has arisen because different products contain varying amounts of three different active hormones isolated from the thymus: thymulin (also known as facteur thymique serique or FTS(, thymopoietin and thymosin alpha 1. Two other partially purified active sybstances, thymosin fraction V and thymostimulin (TP-1), also contain constituents of lymphocytes and epithelial cells in addition to one of the thymic hormones (Hadden 89). The shortest active thymus fraction producing demonstrable activity is an oligopeptide (fraction V) with a molecular weight of 3108 Daltons (Badamchian 97).

Other confusions have arisen due to misleading literature from some companies claiming that their products are hormone free. Commercial preparations, whether liquid or solid, have typically contained at least one of the three thymic hormones because eliminating all of the thymic hormones and other active fractions from the stroma and parenchyma of thymus tissue is a difficult procedure. To the author’s knowledge, none of the commercial preparations claiming to have eliminated the hormone fractions filter out these low weight molecules as it is a costly procedure requiring special filters and equipment and is difficult to achieve on a commercial scale. Purification of one or more of the active fractions, however, has been done successfully on a commercial basis for a number of years. Most of the commercially available thymus fractions are presently derived from bovine thymus, except for thymulin which is derived from porcine serum (Hadden 89). Virtually all of the literature appearing in peer reviewed journals involving the use of thymus extracts have used liquid varieties. No studies using powdered thymus extracts were seen in reviewing papers published in the last 25 years.

Clinical Applications of Thymus Extracts
As mentioned above, the cellular branch of immunity is responsible for vigilance against chronic viruses, fungi, yeast, and parasitic infections as well as neoplasms and aging. Thymus extracts have been used clinically in a variety of ways involving some of these conditions. They have been used orally and as injectables; by themselves and in combination with other therapeutics. Thymus extracts have been used to treat severe and chronic allergies involving the respiratory tract and skin as well as in severe acute and chronic infectious diseases. The extracts have also been shown to reduce post surgical infections, decrease the damage of chemotherapy and radiation and have been used as adjuncts to mainstream therapy for treatment of neoplasms. The review of literature presented below is a survey of the conditions treated using thymus extracts and demonstrates the research completed to date using thymus extracts.

Infections
The effector mechanisms involved in the immune response against infectious agents are mainly macrophages, natural killer (NK) cells, granulocytes, and T and B lymphocytes (Kouttab 89). Clinical improvement depends heavily upon the number and competence of these cells. Hence, cellular immunity is a key to proper recovery from infective states.

Respiratory ailments
Recurrent respiratory infections (RRI) in children

Double blind studies revealed that thymomodulin, a thymus extract, given orally to children was able to reduce the number of RRIs compared to placebo controls and to previous year infections in the same child. An increase in CD3 and CD4 cells, neutrophil functions and salivary IgA levels was also seen (Fiocchi 86). The same extract was also successfully used prophylactically in children with RRI. Continued use prevented relapses of infections and produced an increase in phagocytic responses of alveolar macrophages and serum immunoglobulins (Kouttab 89).

Another calf thymus extract, TFX, was compared to levamisole (Ergamisol), a pharmaceutical immunomodulator, in a placebo controlled trial to treat children suffering from chronic bronchitis. The children chosen for the study had a minimum of 9 months of recurring bronchitis with at least 1 episode per 2 months and were from 19 months to 10 years of age. Both of the treatment groups (TFX and levamisole) showed statistically significant decreases in the number, severity and duration of episodes, and each group required less antibiotic therapy. There was also a tendency toward normalization of the number and function of T lymphocytes in both groups (Skotnicki 89, Radomska 87).

Adult bronchitis
Improvement was also seen in 20 of 26 adults with recurrent upper respiratory tract infections (URI). All subjects were experiencing 8 to 10 severe episodes/year and were resistant to antibiotics, vaccinations, inhalations and other treatments. Each received the thymus extract, TFX, orally daily for 1 month and every second day thereafter for 12 months. Quantitative and/or functional improvements in T lymphocytes were seen in 70% of the patients. These improvement corresponded with clinical improvement manifested by decreased number and severity of episodes, and decreased or no need for antibiotics. One year after treatment was discontinued, patients still reported an improved status. The physician’s conclusion was that thymus extract was "the treatment of choice" as it effectively changed the natural course of the disease by working at the causative level; i.e. the faulty immune process, rather than at the combative (antibiotics) or symptomatic (bronchodilators, etc.) levels (Stankiewiez 86).

Chronic spastic bronchitis
Treatment with TFX thymic extract injections 2x/week for one year used in conjunction with Encortolone [prednisolone (Arizona 93)] (4-12 mg/day) produced clinical improvement and normalization of the granulocyte phagocytic index, but did not alter the defective response in granulocyte migration tests (MIF) (Matusiewicz 87). The author attributed the lack of change to the immunosuppressive effect of the steroid. Similar results were found in other studies (Gieldanowski 81, Smogorzewski 84) confirming that thymus extracts can yield a greater clinical benefit in pulmonary infections than steroids by themselves. Although response is greater and complications fewer, lasting improvement should not be expected when used in conjunction with immunosuppressive steroids.

Bronchial asthma in patients with atopic determatitis
One-hundred-and-sixty-three patients treated for bronchial asthma with the thymus extract, vilozen, showed improvement in clinical signs and symptoms as well as T cell activity. The substance was said by the author to correct the immune disorder (Kogosova 90). Orally administered thymomodulin improved clinical symptoms and reduced the frequency of acute allergic episodes as well as decreased IgE titers and eosinophil counts (Kouttab 89, Fiocchi 87) in patients suffering from combined bronchial asthma and atopic determatitis (Bagnato 89).

Thymus extracts have also been used with patients suffering from combined bronchial asthma and atopic dermatitis to help counterbalance the unfavorable environmental effects of living in polluted air caused by a large industrial power plant. The treatment helped raise immune responsiveness of these patients and significantly increased treatment efficacy of bronchial dilators (Gregor’ev 89).

Chronic Respiratory Infections
Angina & bronchitis

Eighty-six patients with angina and concomitant bronchitis received antibiotics, splenin (a spleen extract) and vilozen (a thymus extract) in a clinical trial. They were compared to 52 controls who received routine treatment. [Routine treatment for angina is typically nitroglycerin under the tongue upon attack. Treatment for bronchitis is rest, fluids and antipyretic and/or analgesic drugs (Berkow 92, p 504 & 658 respectively)]. The results revealed that a combination of splenin and vilozen produced a pronounced fortification of the immune response in the treated group, consequently improving their clinical status. The authors recommend that immunomodulators (thymus and spleen extracts) are indicated in the treatment of repeat and relapsing angina, especially in the presence of comcomitant bronchitis (Frolov 92).

Chronic obstructive pulmonary disease (COPD)

COPD is the combination of chronic obstructive bronchitis and emphysema (Berkow 92, p358). The imbalance of phagocyte functions in COPD include a reduction in PMNs (polymorphonuclear leukocytes) and monocyte chemotaxis and a decreased killing capacity due primarily to a reduced myloperoxide capacity of these cells.

A prospective randomized trial was completed on 78 patients with COPD. Thirty-eight patients were given the thymus extract, thymostimulin (TP-1), intramuscularly (1mg/kg/day) for the first week followed by once per week for 6 months, in addition to the standard treatment for COPD. Patients receiving thymostimulin showed statistically fewer exacerbations and hospital visits during the one year follow-up period compared to the 40 controls receiving standard treatment only. However, there was no change in the number of patients with severe or moderate impairment of respiratory function. Also, there were no changes in serum immunoglobulin or T cell subsets (Banos 97).

In another study, patients suffering from COPD were given thymostimulin (TP-1) for one year and assessed during and after the trial period. The results showed a return to normal of myloperoxide capacity. Phagocyte functional capacities, however, were unaffected. A significant improvement of clinical status was also seen during the one-year program. Because of the laboratory and clinical improvement seen, the authors suggest that thymostimulin be considered in the treatment of COPD (Tortorella 92).

Diseases and Infections of Viral Origin
Tuberculosis

Thirty older patients with active tuberculosis were given the thymus extract t-activin (tactivin) as part of a multimodal therapeutic regimen. The results showed an elevation of T helper cells, enhancement of lymphocyte activity and increased IL-2 synthesis. Enhancement of natural killer cell activity and IL-1 synthesis by macrophages were also observed. This normalization of specific and nonspecific immune responsiveness paralleled clinical improvement (Adambekov 98).

The same thymus extract appeared to benefit a group of patients suffering from pulmonary tuberculosis and type 1 diabetes mellitus combined. Overall, patients with these combined illnesses indirectly showed more depression of cellular immunity, as indicated by a decrease in the number of T-lymphocytes and decreased blast-cell transformation, than those with tuberculosis alone. When t-activin was added to the drug therapy regime, immune parameters normalized. The author also noted a more rapid recovery and more frequent incidence of recovery from tuberculosis in the treated group. They suggested t-activin be added to the therapeutic regimen of patients suffering from type I diabetes and tuberculosis. The authors also noted a more frequent and rapid recovery from tuberculosis in the treated group. As a result of the study, they suggested considering the addition of immunomodulators such as t-activin as part of the therapeutic regimen in type I diabetic patients with tuberculosis (Karachunski 97).

Herpes simplex (HSV)
Herpes simplex is a virus belonging to the herpesvirus group. Herpes simplex type 1 (herpes labialis, cold sores or fever blisters) is transmitted primarily via oral or respiratory routes. Herpes simplex type 2 (herpes genitalia) is transmitted primarily by sexual contact (Tortora 86, p536-7). The virus remains dormant in the skin or nerve ganglia until triggered by over exposure to sunlight, physical or emotional stress, or certain foods or drugs (Berkow 87). If immunity is not established early in the course of the disease, infection is usually lifelong. The thymus extract, TFX, was used to successfully treat 8 patients suffering from recurrent herpes simplex labialis. Patients received the extract every second day for the first month, then twice weekly for 12 months. No reoccurrences were seen during the 12 months in 3 patients who had previously averaged 5 to 10 outbreaks per year. Clinical improvement was noted in 5 others. Frequency, duration and severity of reoccurrence were all substantially reduced while taking the extract. Cessation of the treatment, however, was associated with a return to the previous characteristics of the illness (Skotnicki 89).

Herpes zoster
Herpes zoster is another herpes-type virus that causes chicken pox and shingles (Tortora 86, p534). Although usually a self-limiting viral disease, herpes zoster was used as a clinical model to study the effects of thymus extracts in 28 otherwise non-immuno-compromised patients. Results of this double blind trial reported an accelerated rate of wound healing, shorter duration of vesicles, shorter time to first and full crusting lesions, as well as a greater amelioration of pain during the acute phase (Skotnicki 89). Thus, thymic extracts were shown to be effective in treating viral infections in non-immuno-compromised subjects. This was further underscored in a study treating 5 cases of recurrent human papilloma virus (HPV) where each patient received thymostimulin therapy IM for 9 months. The results showed a reduction in size and number of lesions (Grismondi 91). Note that this is a disease not thought to result from a deficient immune function, yet treatment with thymus extract was beneficial.

Acute and chronic hepatitis B
Hepatitis B is caused by the hepatitis B virus (HBV) and is associated with a wide spectrum of liver diseases, including a subclinical carrier state, acute hepatitis, chronic hepatitis, cirrhosis and hepatocellular carcinoma. Chronic Hepatitis B occurs in 5-10% of patients who initially contracted acute hepatitis B infections (Berkow 92, p902).

Acute hepatitis B: Significant decreases were seen in total bilrubin and iron levels in conjunction with more rapid clinical improvement and shorter hospitalization time in a group of 15 patients with laboratory confirmed acute hepatitis. Patients were given 15 injections of the thymus extract, TFX, beginning the day of diagnosis and followed over the course of the disease until recovery (Kicka 86).

Chronic hepatitis B: Chronic hepatitis B is a difficult disease to treat and has a varying prognosis. Only about 1/3 of the cases develop from acute hepatitis. Most develop insidiously de novo (Berkow 92, p905). The disease has varying courses. "Mild persistent hepatitis, full blown chronic active hepatitis with eventual cirrhosis, and a sub-clinical chronic carrier state all occur. The latter is especially prone to lead ultimately to hepato-cellular carcinoma" (Berkow 92, p903). Illnesses associated with HBV tend to progress and are usually relatively resistant to therapy (Berkow 92, p906). With present medical therapy, patients usually live several years, but hepatocellular failure, cirrhosis, or both eventually develop in many cases (Berkow 92, p906).

The liver injury in HBV is due to an immune mediated host reaction to the infection and not the infection per se (Berkow 92, p905). The use of thymus extracts to normalize the aberrant immune responses seen in hepatitis B is a logical treatment choice.

Consistent with this line of reasoning, 18 patients with biopsy proven chronic active hepatitis B and a lowered T4/T8 ratio received thymic extract TFX for 6 and 12 months in two different groups (Dworniak 91). Improvement in the T4/T8 ratio was seen beginning 14 days after treatment had begun, followed by a decrease in the abnormally high NK cell count. As the NK cell count decreased, NK cell migration and killing activity increased to normal in both the 6 and 12 month groups. Normalization of biochemical and immunological parameters occurred within 5-6 months of beginning treatment. Seroconversion of HBe system to antiHBe was observed after 9-12 months in both of the treatment groups. HBe is a blood marker for presence of the virus core. It indicates active viral replication. Seroconversion to anti-HBe (the antibody to HBe) indicates the virus has ceased replication. This seroconversion usually portends a benign outcome (Berkow 92, p906). A two year follow up showed continued clinical remission with normal immunological and biochemical panels in both groups. The authors conclude that the thymus extract had an immunostimulatory action of lasting duration. A similar study using TFX for 6 months on 29 patients produced similar findings with similar conclusions (Zeman 91).

In another study, thymomodulin thymus extract was administered orally as a syrup at a dose of 120 mg/day for 1 year to a group of children with chronic hepatitis B who had a positive HBs Ag and HBe b Ag blood profile. The results showed a higher rate of recovery and seroconversion to anti-HBe than controls (Bortolotti 88, Raymond 98).

Other liver diseases including chronic cholestatic hepatitis and primary biliary cirrhosis have been successfully treated by the thymus extract, t-activin. Results of a study using 102 patients with chronic cholestatic hepatitis and primary biliary cirrhosis showed an increase in T lymphocytes, increased functional activity of mononuclear cells (increased chemotaxis and inhibition), and decreased immunoglobulin counts. All of these indicators signify an increased immune competence which favors controlling the immuno-inflammatory process in the liver and a normalization of the clinical manifestation of the disease leading to a favorable outcome (Radchenko 92). These results are important not only for the successful treatment of a very difficult disease which frequently has an unfavorable outcome, but also for the implications for treatment of hepatitis produced by other causes. Many of the inflammatory conditions of the liver are caused by viruses, fungi, or mycobacteria (tuberculosis) (Berkow 92, p898). Cellular immunity is the chief defense against these agents. Successful treatment of the above conditions using thymus extracts suggests many exciting possibilities for treatment of presently untreatable ailments of the liver using immunomodulating substances such as thymus extracts.