Skip to main content

Thymomodulin: biological properties and clinical applications

Abstract

Thymomodulin (Ellem Industria Farmaceutica s.p.a., Milan, Italy) is a calf thymus acid lysate derivative, composed of several peptides with a molecular weight range of 1–10 kD. Thymomodulin did not exhibit any mutagenic effect. Furthermore, thymomodulin used in animal studies showed no toxicity even when used at high concentrations. Of major significance are the observations in murine and human systems that thymomodulin remains active when administered orally.In vitro andin vivo administered thymomodulin was able to induce the maturation of T-lymphocytes. Additionally, studiesin vitro showed that this thymic derivative can enhance the functions of mature T-lymphocytes with cascading effects on B-cell and macrophage functions.

Extensive human clinical trials with thymomodulin showed that this agent can improve the clinical symptoms observed with various disease processes, including infections, allergies and malignancies, and can improve immunological functions during ageing.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    Secchi C, Berrini A, Russo V: Caratterizzazione elettroforetica di un fattore timico ad attività immunomielomodulatrice.Eur Rev Med pharmac Sci 4, 499 (1982).

    CAS  Google Scholar 

  2. 2.

    Cazzola P, Mazzanti P, Kouttab N M: Update and future perspectives of a thymic biological response modifier (thymomodulin).Immunopharmac Immunotoxicol 9, 195 (1987).

    Article  CAS  Google Scholar 

  3. 3.

    Cantelli Forti G, Hrelia P, Scotti M, Scornavacche V, Prada M: Mutagenicity studies on thymomodulin.Arzneim-Forsch 37, 1269 (1987).

    Google Scholar 

  4. 4.

    Twomey J J, Kouttab N M: Selected phenotypic induction of null lymphocytes from mice with thymic and nonthymic agents.Cell Immun 72, 186 (1982).

    Article  CAS  Google Scholar 

  5. 5.

    Segatto O, Berrini A, Cuomo M, Natali P G, Secchi C: Thy 1.2 inducing activity of a partially purified calf thymus acid lysate.Int J Immunother 2, 309 (1986).

    CAS  Google Scholar 

  6. 6.

    Segatto O, Viora M, Carsetti R, Di Filippo F, Marcelletti C, Natali P G:In vitro modulation of T-cell differentiation antigens on human thymocytes and splenocytes by a calf thymus acid lysate.Int J Immunother 2, 301 (1986).

    CAS  Google Scholar 

  7. 7.

    Park H M: The recovery of T cell blast transformation in patients with gastrointestinal malignancy by calf thymus components.J Catholic Med College, Korea 37, 1 (1984).

    Google Scholar 

  8. 8.

    Colizzi V, Cazzola P, Mazzanti P: The combined administration of thymomodulin and interleukin 2 reverses T-cell unresponsiveness in mice infected withMycobacterium bovis-BCG.Int J Immunopharmac 10, 271 (1988).

    Article  CAS  Google Scholar 

  9. 9.

    Poli G, Secchi C, Bonizzi L, Guttinger M: Stimulation of the antibody response after treatment with thymomodulin in mice immunodepressed with cyclophosphamide and in aging mice.Int J tiss Reac 8, 231 (1986).

    CAS  Google Scholar 

  10. 10.

    Montagna D, Maccario R, Mazzanti P, Cazzola P, Nespoli L: Thymomodulin enhancesin vitro natural killer (NK) activity of human cord blood lymphocytes (CBL).Thymus 11, 201 (1988).

    PubMed  CAS  Google Scholar 

  11. 11.

    Kouttab N M, Twomey J J: The pharmacodynamics ofin vivo administered thymomodulin.Drugs exp clin Res 10, 921 (1984).

    CAS  Google Scholar 

  12. 12.

    Calsini P, Mocchegiani E, Fabris N: The pharmacodynamics of Thymomodulin in elderly humans.Drugs exp clin Res 11, 671 (1985).

    PubMed  CAS  Google Scholar 

  13. 13.

    Andolina M, Dobrinz M G, Meraviglia L, Agosti E, Cazzola P: Myelopoiesis induction on human bone marrow precursor cells by a calf thymic derivative (thymomodulin):in vitro comparison with exogenous CSF.Int J Immunother 3, 139 (1987).

    CAS  Google Scholar 

  14. 14.

    Uray Z, Imreh S, Suciu D, Maniu M, Banu C: Influence of thymic humoral factor(s) on haemopoiesis in mice.Radiosensitiz Newslett, Japan 4, 1 (1985).

    Google Scholar 

  15. 15.

    Ferrero M E, Marni A, Gaja G, Tiengo M, Cazzola P: A calf thymus lysate (thymomodulin)in vitro restores impaired cellular metabolism induced by isoflurane.J Drug Devel 1, 55 (1988).

    Google Scholar 

  16. 16.

    Gilman S C, Lewis A J: Immunopharmacological approaches to drug development, in Williams M, Malick J B (eds):Drug Discovery and Development, p. 227. Clifton, NJ, The Humana Press, (1987).

    Google Scholar 

  17. 17.

    Werner G H, Floc’h F, Migliore Samour D, Jollès P: Immunomodulating peptides.Experientia 42, 521 (1986).

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    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 42, 1011 (1987).

    Google Scholar 

  19. 19.

    Blumberg R S, Schooley R T: Lymphocyte markers and infectious diseases.Sem Hemat 22, 81 (1985).

    CAS  Google Scholar 

  20. 20.

    Drews J: The experimental and clinical use of immune modulating drugs in the prophylaxis and treatment of infections.Infection 12, 157 (1984).

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Masihi K N, Lange W, Lotzovà E: Highlights of the International Symposium on Immunomodulators and Nonspecific Defense Against Microbial Infections.Natn Immun Cell Growth Regul 6, 213 (1987).

    Google Scholar 

  22. 22.

    Shackelford P G, Palmar S H, Mayus J L, Johnson W L, Corry J M, Nahm M H: Spectrum of IgG2 subclasses deficiency in children with recurrent infections: prospective study.J Pediatr 108, 647 (1986).

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Hakansson L, Foucard T, Hallgren R, Venge P: Neutrophil function in infection-prone children.Arch dis Child 55, 776 (1980).

    PubMed  CAS  Article  Google Scholar 

  24. 24.

    Bondestam M, Funa K, Alm G V: Defective leukocyte interferon response in children with recurrent infections accompanied by arthralgia.Acta Paediatr scand 74, 219 (1985).

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Fiocchi A, Borella E, Riva E, Arensi D, Travaglini P, Cazzola P, Giovannini M: A double-blind clinical trial for the evaluation of the therapeutical effectiveness of a calf thymus derivative (Thymomodulin) in children with recurrent respiratory infections.Thymus 8, 331 (1986).

    PubMed  CAS  Google Scholar 

  26. 26.

    Clerici Schoeller M, Careddu P, Sandri M T, Cazzola P: Recurrent respiratory infections in children: prevention of acute episodes by oral administration of a thymic derivative (Thymomodulin).Curr Ther Res, in press.

  27. 27.

    Weitzenblum E: Acute respiratory failure in the patient with obstructive airways disease, inFishman A P (ed):Pulmonary Diseases and Disorders, p. 2287. New York, McGraw-Hill (1988).

    Google Scholar 

  28. 28.

    Sofia M, Molina A, Mormile M, De Simone F, Carratù L: Studio in doppio cieco sull’efficacia della Timomodulina per orale via nella prevenzione delle riacutizzazioni in corso di bronchite cronica.G ital Mal Torace 41, 339 (1987).

    Google Scholar 

  29. 29.

    Maiorano V, Chianese R, Fumarulo R, Costantino E, Contini M, Carnimeo M, Mazzanti P, Cazzola P: The use of an immunomodulator (thymomodulin) in recurrent respiratory infections: control with FOB and BAL.Abs. 6th Congress of the European Society of Pneumology. Amsterdam 31st Aug.–5th Sep. 1987, p. 389.

  30. 30.

    Gordon J, Nohr C, Rode H, Christou N, Meakins J L: Anergic surgical patients have an acquired, transient immunodeficiency of unknown etiology, in:Viral Mechanisms of Immunosuppression, p. 89. New York, Alan R. Liss (1985).

    Google Scholar 

  31. 31.

    Terrizzi A, Di Somma C, Dato D, Sandri M T, Cazzola P, Berti Riboli E: Thymomodulin prevents post-operative immunedepression measured by means of skin tests.Int J Tiss Reac, in press.

  32. 32.

    Eggkin H F, Houthoff H K, Huitema S, Wolters G, Poppema S, Gips C H: Cellular and humoral immune reactions in chronic active liver disease. II. Lymphocyte subsets and viral antigen in liver biopsies of patients with acute and chronic hepatitis B.Clin exp Immun 56, 121 (1984).

    Google Scholar 

  33. 33.

    Lemm G, Salzer K, Warnatz H: Studies on immunoregulatory mechanisms in acute and chronic hepatitis B.Clin exp Immun 52, 250 (1983).

    PubMed  CAS  Google Scholar 

  34. 34.

    Galli M, Crocchiolo P, Negri C, Caredda F, Lazzarin A, Moroni M: Attempt to treat acute type B hepatitis with an orally administered thymic extract (Thymomodulin): preliminary results.Drugs exp clin Res 11, 665 (1985).

    PubMed  CAS  Google Scholar 

  35. 35.

    Edgington T S, Chisari F V: Immunological aspects of hepatitis B virus infection.Am J med Sci 270, 213 (1985).

    Article  Google Scholar 

  36. 36.

    Fattovich G, Rugge M, Brollo L, Pontisso P, Noventa F, Guido M, Alberti A, Realdi G: Clinical virology and histologic outcome following seroconversion from HBeAg to anti-HBe in chronic hepatitis type B.Hepatology 6, 167 (1986).

    PubMed  Article  CAS  Google Scholar 

  37. 37.

    Bortolotti F, Cadrobbi P, Crivellaro C, Armigliato M, De Manzini A, Lepore L, Carrara F, Realdi G: Effect of an orally administered thymic derivative, Thymomodulin, in chronic type B hepatitis in children.Curr Ther Res 43, 67 (1988).

    Google Scholar 

  38. 38.

    Fauci A S: Immunologic abnormalities in the acquired immunodeficiency syndrome (AIDS).Clin Res 32, 491 (1984).

    PubMed  CAS  Google Scholar 

  39. 39.

    Valesini G, Barnaba V, Benvenuto R, Balsano F, Mazzanti P, Cazzola P: 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 23, 1915 (1987).

    PubMed  Article  CAS  Google Scholar 

  40. 40.

    Strannegard O, Strannegard I L: T lymphocyte numbers and function in human IgE-mediated allergy.Immun Rev 41, 149 (1978).

    PubMed  Article  CAS  Google Scholar 

  41. 41.

    Kus J, Tse K S, Enarson D, Grzybowsky S, Chan-Yeung M: Lymphocyte sub-population in patients with allergic rhinitis.Allergy 39, 509 (1984).

    PubMed  Article  CAS  Google Scholar 

  42. 42.

    Marzari R, Mazzanti P, Cazzola P, Pirodda E: Rinopatia allergica perenne. Profilassi degli episodi acuti mediante l’impiego di Timomodulina.Miner Med 78, 1675 (1987).

    CAS  Google Scholar 

  43. 43.

    Genova R, Guerra A: Un estratto di timo (Timomodulina) nella profilassi dell’asma infantile.Ped Med Chir 5, 395 (1983).

    CAS  Google Scholar 

  44. 44.

    Genova R, Guerra A: Thymomodulin in management of food allergy in children.Int J Tiss Reac 8, 239 (1986).

    CAS  Google Scholar 

  45. 45.

    Fiocchi A, Grasso U, Rottoli A, Travaglini P, Mazzanti P, Cazzola P, Giovannini M: A double blind clinical trial on the effectiveness of a thymic derivative (thymomodulin) in the treatment of children with atopic dermatitis.Int J Immunother 3, 279 (1987).

    Google Scholar 

  46. 46.

    Di Luciano G, Cosentino M, Catapano A, Maccarone C, Pattarello M, Mazzanti P, Cazzola P: Associazione immunoterapia specifica-timomodulina in corso di asma bronchiale allergico.Farmac Terap 4, 286 (1987).

    Google Scholar 

  47. 47.

    Herberman R B: Cancer therapy by biological response modifiers.Clin Physiol Biochem 5, 238 (1987).

    PubMed  CAS  Google Scholar 

  48. 48.

    Campbell A C, Hersey P, Harcling B, Hollingsworth P M, Skinner J, Maclennan J C M: Effects of anticancer agents on immunological status.Br J Cancer 28, 254 (1973).

    CAS  Google Scholar 

  49. 49.

    Reizenstein P, Mathé G, Vriz N, Lomme L: Nonspecific immunomodulators in oncology and hematology, in Oldham R K (ed):Principles of Cancer Biotherapy, p. 163. New York, Raven Press (1987).

    Google Scholar 

  50. 50.

    Edery A, Alvarez R, Valentini J, Fernandez A, Cazzola P, Mazzanti P: Prevencion de la leucopenia por irradiacion mediante el empleo de Timomodulina.Semana Med 171, 282 (1987).

    Google Scholar 

  51. 51.

    Gallo Curcio C, Barduagni A, Tonachella R, Tropea F, Terzoli E: Double blind randomized study on the effect of Thymomodulin in chemoinduced myelodepression in cancer patients: preliminary results.Int J Immunother 2, 189 (1986).

    Google Scholar 

  52. 52.

    Kang S D, Lee B H, Yang J H, Lee C Y: The effects of calf-thymus extract on recovery of bone marrow function in anticancer chemotherapy.New Med J, Kor 28, 11 (1985).

    Google Scholar 

  53. 53.

    Kim C C: The augmentation of lymphocyte blast transformation in patients with malignancy by Thymomodulin.Kor J Hemat 20, 1 (1985).

    Google Scholar 

  54. 54.

    Weksler M E: The senescence of the immune system.Hosp Pract 16, 53 (1981).

    CAS  Google Scholar 

  55. 55.

    Steinmann G G: Changes in the human thymus during ageing, in Muller-Hermelink H K (ed):The Human Thymus. Histophysiology and Pathology, p. 43. Berlin, Springer (1986).

    Google Scholar 

  56. 56.

    Bach J F, Dardenne M, Pleau J M, Bach M A: Isolation, biochemical characterization and biological activity of circulating thymic hormone in the mouse and in the human.Ann NY Acad Sci 248, 186 (1975).

    Article  Google Scholar 

  57. 57.

    Goldstein A L, Hooper J A, Schulof R S, Cohen G H, Thurman G B, McDaniel M C, White A, Dardenne M: Thymosin and the immunopathology of aging.Fedn Proc Fedn Am Soc exp Biol 33, 2053 (1974).

    CAS  Google Scholar 

  58. 58.

    Francini F, Belief M T, Bacigalupo A, Resnik P: Estudio de la acciòn immuno-estimulante de la timomodulina en geriatria.Orient Med 1330, 108 (1986).

    Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to N. M. Kouttab.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kouttab, N.M., Prada, M. & Cazzola, P. Thymomodulin: biological properties and clinical applications. Med. Oncol. & Tumor Pharmacother. 6, 5–9 (1989). https://doi.org/10.1007/BF02985217

Download citation

Keywords

  • Atopic Dermatitis
  • Food Allergy
  • Allergic Rhinitis
  • Biological Response Modifier
  • Recurrent Respiratory Infection