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Clinical Immunotherapeutics

, Volume 1, Issue 5, pp 378–398 | Cite as

Thymostimulin

A Review of its Pharmacology and Prospective Role in Immunotherapy
  • Kerry L. Dechant
  • Harriet M. Bryson
Drug Evaluation

Summary

Synopsis

Thymostimulin is a partially purified extract of calf thymus which stimulates T cell proliferation and differentiation. Initial evidence suggests that thymostimulin reduces the incidence of infection in at-risk patients including those undergoing surgery, patients with cancer, or those with chronic or recurrent infections. In patients with cancer, reduction of chemotherapy-induced myelosuppression with thymostimulin may permit more aggressive chemotherapy and/or radiotherapy. Few adverse events have been described in association with thymostimulin therapy, although the tolerability profile of thymostimulin cannot yet he considered established. Isolated cases of severe anaphylaxis have been reported.

In summary, thymostimulin shows promise as an immunomodulatory agent, capable of restoring T cell function in immunocompromised patients. However, full characterisation of the active component(s) of thymostimulin, and its pharmacokinetic, dose-response and tolerability profile is needed before the role of this agent can be fully established.

Pharmacological Properties

Thymostimulin, a partially purified extract of calf thymus, improves the number and function of T cells, the primary effectors of cell-mediated immunity. In vitro studies in mouse spleen lymphoid cells and in lymphocytes from immunocompromised patients show that thymostimulin enhances proliferation and differentiation of T helper cells, and induces production of lymphokines, particularly interleukin-2 and interferon-γ.

In vivo, thymostimulin restores immune system function in animals in which immunity has been spontaneously or experimentally impaired.

The ability of thymostimulin to improve parameters of cell-mediated immunity has also been demonstrated in humans with primary or secondary immunodeficiencies. Thymostimulin improved many indices of immune function, including T helper cell number and function, and the activities of peripheral phagocytes, natural killer cells and other peripheral lymphokine-activated cells. In some studies, thymostimulin has been shown to enhance interleukin-2 and interferon-γ activity, as well as proliferation of peripheral erythroid progenitor cells. No human pharmacokinetic data are available concerning thymostimulin.

Therapeutic Potential

Several studies have demonstrated that thymostimulin, coadministered with antibiotic prophylaxis, significantly reduces the rate of postoperative infection in patients undergoing various types of surgery compared with antibiotic prophylaxis alone. However, conflicting results concerning the efficacy of thymostimulin were obtained in patients most at risk of postoperative infections (anergic patients); further studies in anergic patients using higher doses of thymostimulin are warranted.

Studies in patients with various cancers demonstrated that thymostimulin may counteract or ameliorate the myelotoxic and lymphotoxic effects of antineoplastic therapy. Importantly, thymostimulin reduced the incidence of leucopenia and opportunistic infections in some studies, thereby permitting administration of more intensive radio- and/or chemotherapeutic regimens. Objective response rates of 40 to 45% in a total of 31 patients with hepatocellular carcinoma have been reported with thymostimulin monotherapy at 1 centre.

When administered early in the course of disease in patients with the acquired immunodeficiency syndrome (AIDS), thymostimulin protected patients from zidovudine-induced bone marrow toxicity, thereby permitting administration of higher doses of the antiviral therapy. Thymostimulin also reduced the rate of infection recurrence in immunocompromised patients with chronic bacterial (respiratory tract infections) or viral infections.

In addition, thymostimulin has also shown some promise in the treatment of patients with hepatitis B or immunoregulatory disorders including type I diabetes, atopic eczema and idiopathic cytopenias.

Tolerability

Few published tolerability data concerning thymostimulin are available. While thymostimulin has been well tolerated in a number of clinical trials, severe anaphylactic reactions have been reported in individual patients. As a result, intracutaneous tests with bovine proteins prior to thymostimulin administration have been recommended to eliminate the possibility of an allergic reaction to these proteins. Detailed tolerability studies with various doses of thymostimulin and in different patient groups are warranted, as are drug interaction studies, given that thymostimulin is often coadministered with other agents. In particular, the issue of whether or not antibodies develop during long term thymostimulin therapy should be investigated.

Dosage and Administration

Thymostimulin is administered intramuscularly. The recommended starting dosage is 1 mg/kg daily during the first week, followed by the same dose 2 to 3 times weekly thereafter. Treatment duration varies from several weeks to several months or more, depending on the nature and severity of the patient’s condition.

Keywords

Human Immunodeficiency Virus Adis International Limited Atopic Eczema Zidovudine Bovine Spongiform Encephalopathy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Roitt I. Essential Immunology Seventh Edition. Oxford: Black-well Scientific Publications, 1991Google Scholar
  2. 2.
    Skotnicki AB. Thymic hormones and lymphokines. Drugs Today 1989; 25: 337–362Google Scholar
  3. 3.
    Lin C-Y, Kuo Y-C, Lin C-C, et al. Enhancement of interleukin-2 and γ-interferon production in vitro on cord blood lymphocytes and in vivo on primary cellular immunodeficiency patients with thymic extract (thymostimulin). J Clin Immunol 1988; 8: 103–107PubMedCrossRefGoogle Scholar
  4. 4.
    Shoham J. Evaluation of the activity of peptides isolated from the thymic extract TP-1 in vitro. In: Periti P, Crassi GG, editors. Current chemotherapy and immunotherapy, Washington, ASM, 1982: 2, 1185–1187Google Scholar
  5. 5.
    Tan ACITL, Russel FGM, Thien T, et al. Atrial natriuretic peptide: an overview of clinical pharmacology and pharmacokinetics. Clin Pharmacokinet 1993; 24: 28–45PubMedCrossRefGoogle Scholar
  6. 6.
    Wills RJ. Clinical pharmacokinetics of interferons. Clin Pharmacokinet 1990; 19: 390–399PubMedCrossRefGoogle Scholar
  7. 7.
    Falchetti R, Bergesi G, Eshkol A, et al. Pharmacological and biological properties of a calf thymus extract (TP-1). Drugs Exp Clin Res 1977; 3: 39–47Google Scholar
  8. 8.
    Lin C-Y, Chu C-M. In vitro effect of a bovine extract (thymostimulin) on T-cell differentiation in cord blood lymphocytes. Pediatr Pharmacol 1985; 5: 181–187Google Scholar
  9. 9.
    Lin C-Y, Low TLK. A comparative study on the immunological effects of bovine and porcine thymic extracts: induction of lymphoproliferative response and enhancement of interleukin-2, γ-interferon and tumor necrosis factor production in vitro on cord blood lymphocytes. Immunopharmacol 1989; 18: 1–10CrossRefGoogle Scholar
  10. 10.
    Martelli MF, Velardi A, Rambotti P, et al. The in vitro effect of a calf thymus extract thymostimulin on the immunologic parameters of patients with untreated Hodgkin’s disease. Cancer 1982; 49: 245–250PubMedCrossRefGoogle Scholar
  11. 11.
    Petrini M, Polidori R, Azzarà A, et al. Increased PHA response to thymostimulin in the elderly. Curr Ther Res 1981; 30: 367–371Google Scholar
  12. 12.
    Fiorilli M, Ammirati P, Pandolfi F, et al. Richerche immunologiche e cliniche so di un estratto timico bovino (TP-1): effetto sulla differenziazione in vitro dei linfociti in condizioni normali e patologiche. Folia Allergologica et Immunologica Clinica 1977; 24: 15–23Google Scholar
  13. 13.
    Shoham J, Cohen M, Chandali Y, et al. Thymic hormonal activity on human peripheral lymphocytes, in vitro. I. Reciprocal effect on T and B rosette formation. Immunol 1980; 41: 353–359Google Scholar
  14. 14.
    Fiorilli M, Ammirati P, Pandolfi F, et al. Immunological and clinical investigation of a bovine thymic extract. I. In vitro effect on T-cell differentiation in normal and pathological conditions. Ann Sclavo 1979; 21: 494–501PubMedGoogle Scholar
  15. 15.
    Shoham J. Eshel I, Aboud M, et al. Thymic hormonal activity on human peripheral blood lymphocytes, in vitro. II. Enhancement of the production of immune interferon by activated cells. J Immunol 1980; 125: 54–58PubMedGoogle Scholar
  16. 16.
    Shoham J, Eshel I. Thymic hormonal effect on human peripheral blood lymphocytes, in vitro. III. Conditions for mixed lymphocyte-tumor culture assay. Journal of Immunol Methods 1980; 37: 261–273CrossRefGoogle Scholar
  17. 17.
    Shoham J, Eshel I. Thymic hormonal activity on human peripheral blood lymphocytes, in vitro. IV. Proliferative response to allogeneic tumor cells in healthy adults and cancer patients. Int J Immunopharmacol 1983; 5: 515–522PubMedCrossRefGoogle Scholar
  18. 18.
    Liberati AM, Cinieri S, Fizzotti M, et al. Modulation of NK activity by thymic hormones: in vitro effects of thymostimulin. Med Oncol Tumor Pharmacother 1989; 6: 45–52PubMedGoogle Scholar
  19. 19.
    Moltó LM, Carballido JA, Manzano L, et al. Thymostimulin enhances the natural cytotoxic activity of patients with transitional cell carcinoma of the bladder. Int J Immunopharmacol 1993; 15: 335–341PubMedCrossRefGoogle Scholar
  20. 20.
    Falchetti R, Caprino L, Cafiero C. Enhancement of the immunocompetence in neonatal guinea pigs by a thymic factor (TS). Thymus 1981; 2: 215–224PubMedGoogle Scholar
  21. 21.
    Falchetti R, Cafiero C, Caprino L. Impaired T-cell functions in aged guinea-pigs restored by thymostimulin (TS). Int J Immunopharmacol 1982; 4: 181–186PubMedCrossRefGoogle Scholar
  22. 22.
    Klein AS, Fixier R, Shoham J. Antiviral activity of a thymic factor in experimental viral infections. I. Thymic hormonal effect on survival, interferon production and NK cell activity in Mengo virus-infected mice. J Immunol 1984; 132: 3159–3163PubMedGoogle Scholar
  23. 23.
    Bistoni F, Baccarini M, Puccetti P, et al. Enhancement of natural killer cell activity in mice by treatment with a thymic factor. Cancer Immunol Immunother 1984; 17: 51–55PubMedCrossRefGoogle Scholar
  24. 24.
    Yagi M, Yamashita T, Tsubura E. Effect of a thymic factor, thymostimulin, on growth and pulmonary metastases of Lewis lung carcinoma. Cancer Immunol Immunother 1985; 19: 198–204PubMedCrossRefGoogle Scholar
  25. 25.
    Klein AS, Lang R, Eshel I, et al. Modulation of immune response and tumor development in tumor-bearing mice treated by the thymic factor thymostimulin. Cancer Res 1987; 47: 3351–3356PubMedGoogle Scholar
  26. 26.
    Klein AS, Schreiber R, Shoham J. Effect of thymic extract thymostimulin (TP-1R) on immune response of mice with prolonged immunosuppression induced by the cytotoxic drug-CCNU [abstract no. 56]. Int J Immunopharmacol 1982; 4: 297CrossRefGoogle Scholar
  27. 27.
    Falchetti R, Cafiero C, Diorio U, et al. Thymostimulin (TS) effects on immunological responses of cyclophosphamide treated newborn guinea pigs. Abstract 65. Int J Immunopharmacol 1982; 4: 300CrossRefGoogle Scholar
  28. 28.
    Montoya JA, Martínez EM, Rodríguez M, et al. Immunochemotherapy (thymostimulin/cyclophosphamide) in dogs. Br Vet J 1990; 146: 249–254PubMedCrossRefGoogle Scholar
  29. 29.
    Balleari E, Massa G, Musselli C, et al. In vivo effects of thymostimulin on hematopoiesis of mice treated with cyclophosphamide. Clin Immunol Immunopathol 1993; 68: 363–367PubMedCrossRefGoogle Scholar
  30. 30.
    Cainzos M, Paulos A, Novás S, et al. Effect of thymostimulin on the restoration of delayed hypersensitivity in jaundiced and anergic rats [abstract no. 25]. Proceedings of the Annual Meeting of the Surgical Infection Society of Europe; 1993 Jun 3–5: VareseGoogle Scholar
  31. 31.
    Garcia-Valdecasas JC, Martinez A, Lopoez-Boado MA, et al. Peripheral blood lymphocyte changes after benign gastrointestinal surgery. Role of thymostimulin in reversing the postoperative immunodepression seen in humans. Hepato-gastroenterology 1988; 35: 219–222PubMedGoogle Scholar
  32. 32.
    Balleari E, Timitilli S, Musselli C, et al. In vivo hemopoietic activity of thymic extract ‘thymustimulin’ in aged healthy humans. Thymus 1992; 19: 59–63PubMedGoogle Scholar
  33. 33.
    Barbaro G, Caremani M, Maestrini R, Sabusco G, Sabitini P, et al. Zidovudine vs zidovudine-thymostimulin association in long term treatment of patients with asymptomatic HIV infection and with progressive generalized lymphadenopathy. The TP1-AZT multicenter study. Ther Infect Dis 1991; 6: 5–14Google Scholar
  34. 34.
    Casale G, Zurita IE, Colombo M, et al. Immunological studies in the aged: effects of a thymic factor (TP-1 Serono®). Drugs Exp Clin Res 1983; 9: 507–511Google Scholar
  35. 35.
    Liberati AM, Brugia M, Edwards BS, et al. Immunorestorative properties of thymostimulin (TS) in patients with Hodgkin’s disease in clinical remission. Cancer Immunol Immunother 1985; 19: 136–141PubMedCrossRefGoogle Scholar
  36. 36.
    Palmisano L, Chisesi T, Galli M, et al. Thymostimulin treatment in AIDS-related complex. Clin Immunol Immunopathol 1988; 47: 253–261PubMedCrossRefGoogle Scholar
  37. 37.
    Pontiggia P, Ogier C, Follini GD. Effect of treatment with thymustimulin (Tp-1) on T and B cells in lymphoproliferative disorders. Blut 1983; 47: 153–156PubMedCrossRefGoogle Scholar
  38. 38.
    Raise E, Bonazzi L, Di Giandomenico G, et al. Thymostimulin treatment in cases of AIDS and ARC. J Exp Pathol 1987; 3: 745–750PubMedGoogle Scholar
  39. 39.
    Romeo F, Arcoria D, Palmisano L, et al. Effectiveness of thymostimulin treatment in hepatitis B surface antigen-positive chronic active liver disease. Results of a randomised clinical trial. Arzneimittel-Forschung 1985; 35: 1317–1322PubMedGoogle Scholar
  40. 40.
    Surico N, Tavassoli K. Trattamento immunostimolante nel carcinoma mammario: gli effetti sul sistema immunitario. European Journal of Medical Updating 1992; 2: 29–38Google Scholar
  41. 41.
    Surico N, Tavassoli K. Timostimolina nel trattamento della malattia infiammatoria pelvica ricorrente. Immunologica Clinica 1993; 12: 21–31Google Scholar
  42. 42.
    Tas M, Leezenberg A, Drexhage HA. Beneficial effects of the thymic hormone preparation thymostimulin in patients with defects in cell-mediated immunity and chronic purulent rhinosinusitis. A double-blind cross-over trial on improvements in monocyte polarization and clinical effects. Clin Exp Immunol 1990; 80: 304–313PubMedCrossRefGoogle Scholar
  43. 43.
    Velardi A, Spinozzi F, Rambptti P, et al. The in vivo effect of thymic factor (thymostimulin) administration on circulating immune complexes and serum lysozyme levels in untreated Hodgkin’s disease patients. J Clin Oncol 1983; 1: 117–125PubMedGoogle Scholar
  44. 44.
    Lersch C, Zeuner M, Bauer A, et al. Palliative chemoimmunotherapy with low doses of cyclophosphamide (LDCY), echinacea purpurea extracts (echinacin) and thymostimulin in outpatients with far advanced pancreatic malignancies. A preliminary report. J Exp Clin Res 1990; 9: 247–250Google Scholar
  45. 45.
    Lersch C, Zeuner M, Bauer A, et al. Stimulation of the immune response in outpatients with hepatocellular carcinomas by low doses of cyclophosphamide (LDCY), echinacea purpurea extracts (echinacin) and thymostimulin. Arch Geschwulstforsch 1990; 60: 379–383PubMedGoogle Scholar
  46. 46.
    Lersch C, Zeuner M, Bauer A, et al. Stimulation of immunocompetent cells in patients with gastrointestinal tumors during an experimental therapy with low doses of cyclophosphamide (LDCY), thymostimulin and echinaceae purpureae extracts (echinacin). Tumordiagn u Ther 1992; 13: 115–120Google Scholar
  47. 47.
    Periti P, Tonelli F, Mazzei T, et al. Antimicrobial chemo-immunoprophylaxis in colorectal surgery with cefotetan and thymostimulin: prospective, controlled multicenter study. J Chemother 1993; 5: 37–42PubMedGoogle Scholar
  48. 48.
    Allone T, Caldarola B, Gallo G, et al. L’immunoprofilassi delie infezioni chirurgiche in pazienti immunodepressi. In Italian. Giornate Medico Chirurgiche Internazionali. 1991; 527–533, December 8–14: TorinoGoogle Scholar
  49. 49.
    Amodeo C, Missiato A, Pulvirenti A, et al. The immuno-prophylaxis with thymostimulin in surgical risk patients. Surg Immunity 1990; 3: 13–16Google Scholar
  50. 50.
    Calvo M, Muñoz-Calero A, Louredo A, et al. Immuno-prophylaxis of infection in gastrointestinal oncological surgery [Translated into English from Spanish]. Cir Esp 1993 Suppl. 1: 75Google Scholar
  51. 51.
    Cocimano V, Casetta G, Piana P, et al. Incidence of urinary tract infections following endoscopic surgery in immunodepressed patients treated with thymostimulin. J Exp Pathol 1987; 3: 607–611PubMedGoogle Scholar
  52. 52.
    Farina EC, Garino M, Balbo G. Thymostimulin prophylaxis of postoperative infections in anergic patients. Can J Surg 1986; 29: 445–446PubMedGoogle Scholar
  53. 53.
    Farina EC, Garino M, Resegotti A, et al. The control of postoperative infections in neoplastic patients [Translated into English from Italian]. XVII Congresso Nazionale Società Italiana di Chirurgia Oncologica; 1993 Sep 19–21: Napoli. 1993: 53–60Google Scholar
  54. 54.
    Maffei Faccioli A, Manfè AZ, et al. The possibility of immunomodulation in the surgical patient [Translated into English from Italian]. Archivio ed atti delia Società Italiana di Chirurgia 1990 Oct 21–25: Rome. 265–269, 1990Google Scholar
  55. 55.
    Perotti F, Landi G, Primatesta F, et al. Immunoprofilassi con timostimolina in chirurgia addominale d’elezione. Minerva Chir 1992; 47: 1091–1093PubMedGoogle Scholar
  56. 56.
    Raule M, Alemanno R, Marinoni M, et al. Il rischio infettivo nella chirurgia oncologica del colon retto. Significatività dell’immunomodulazione e della antibiotico-profilassi. Chirurgia 1992; 5: 666–669Google Scholar
  57. 57.
    Rodriguez Ramos M, Romero G, Santamaría R, Sánchez E [abstract]. Immunomodulation with thymostimulin in patients with tumours of the colon and rectum [Translated into English from Spanish]. Cir Esp 1993; 54Suppl. 1: 111Google Scholar
  58. 58.
    Soláns A, Navarro M, Lozano R, et al. Thymostimulin in surgical patients with digestive tract cancer. Second World Week of Professional Updating in Surgery and in Surgical and Oncological Disciplines of the University of Milan; Jul 15–20, 1990; 63–67Google Scholar
  59. 59.
    Terrizzi A, Gipponi M, Meloni C, et al. Use of thymic factor in the prevention of postoperative infections. Ital J Surg Sci 1985l; 15: 243–248PubMedGoogle Scholar
  60. 60.
    Mustacchi G, Italian Cooperative Trials Group. High-dose folinic acid (HDFA) and fluorouracil (FU) plus or minus thymostimulin (TS) for treatment of metastatic colorectal cancer (MCRC): a randomised multicentric study [abstract no. 470]. Eur J Cancer 1993; 29Suppl. 6: S89CrossRefGoogle Scholar
  61. 61.
    Pavesi L, Italian Cooperative Trials Group. Fluorouracil (F), with and without high-dose folinic acid (HDFA) plus epirubicin (E) and cyclophosphamide (C): FEC versus HDFA-FEC plus or minus thymostimulin (TS) in metastatic cancer: results of a multicenter study [abstract no. 401]. Eur J Cancer 1993; 29Suppl. 6: S77CrossRefGoogle Scholar
  62. 62.
    Iaffaioli RV, Frasci G, Tortora G, et al. Effect of thymic extract ‘thymostimulin’ on the incidence of infections and myelotoxicity during adjuvant chemotherapy for breast cancer. Thymus 1988; 12: 69–75PubMedGoogle Scholar
  63. 63.
    Iaffaioli RV, Caponigro F, Facchini G, et al. Immunological and clinical effects of thymostimulin in patients with non small cell lung cancer treated with combined chemotherapy. Drug Invest 1994; 7: 209–214CrossRefGoogle Scholar
  64. 64.
    Negri L, Calabrese F, Correggia F, et al. Chemioterapia e timostimolina nel trattamento della neoplasia mammaria in fase avanzata. Minerva Med 1992; 83: 283–288PubMedGoogle Scholar
  65. 65.
    Cánovas Fernández, González de Zárate P, Alonso Alonso J, et al. La timoestimulina como tratamiento adyuvante a la quimioterapia antineoplástica. Experiencia en pacientes con mieloma y linfoma [In Spanish]. Rev Clin Esp 1988; 183: 340–343Google Scholar
  66. 66.
    Macchiarini P, Danesi R, Del Tacca M, et al. Effects of thymostimulin on chemotherapy-induced toxicity and long-term survival in small cell lung cancer patients. Anticancer Res 1989; 9: 193–196PubMedGoogle Scholar
  67. 67.
    Tomassone W, Tetti M, Quargnali M, et al. Postoperative adjuvant radiotherapy and immunomodulating therapy in stage I and II uterine sarcoma. Recenti Prog Med 1988; 79 Suppl.: 1–2Google Scholar
  68. 68.
    Airoldi M, Gabriele P, Pedani F, et al. Chemotherapy versus chemoimmunotherapy with thymostimulin in advanced oral cavity cancers: clinical results of a randomised study. Recenti Prog Med 1987; 78Suppl. N: 67–70Google Scholar
  69. 69.
    Alba E, Folpini E, Libanon E, et al. Reduction of infectious processes and improvement of well-being in patients treated with thymostimulin (Tp-1, Serono) during chemotherapy for breast cancer [abstract]. Proceedings of the Third International Congress on Infections in Obstetrics and Gynaecology; 1988 May 4–7: PaviaGoogle Scholar
  70. 70.
    Farris A, Bisail M, Sarobba MG, et al. Thymostimulin in combination with chemotherapy in patients with breast cancer. Ter Mod 1990; 4: 1–2Google Scholar
  71. 71.
    Giorgis GE, Galietti F, Massaglia GM, et al. Prevenzione delie micosi orofaringee mediante timostomolina nei pazienti affetti da carcinoma broncogeno inoperabile. Minerva Pneumologica 1991; 30: 133–135Google Scholar
  72. 72.
    Paganelli A, Babilonti L, Bolis PF. Use of thymostimulin in combination with chemotherapy for stage III and IV ovarian cancer. Recenti Prog Med 1987; 78 Suppl.: 1–2Google Scholar
  73. 73.
    Tetti M, Tomassone W, Milani R, et al. Use of an immunomodulatory drug in the prevention of the appearance of urinary tract infectious episodes in patients with gynaecological neoplasia subjected to radiotherapy. Recenti Prog Med 1987; 78Suppl. 6: 1–2Google Scholar
  74. 74.
    Ortiz Gordillo MJ, Alonso Redondo E, Bayo Lozano E, et al. Tratamiento simultáneo con cisplatino y radioterapia en asociación con timoestimulina en carcinoma epidermoide avanzado de cabeza y cuello. Valoració de respuesta y toxicidad. Oncologia 1991; 14: 63–68CrossRefGoogle Scholar
  75. 75.
    Bernengo MG, Doveil GC, Appino A, et al. Thymus hormones in malignant melanoma: personal experiences with thymostimulin (TP-1) and thymopentin (TP-5). In: Nagel et al. editors. Thymus hormones in oncology. 1988; 19: 133–147Google Scholar
  76. 76.
    Montesarchio V, Coponigro F, Leo L, et al. Thymostimulin in the treatment of hepatocellular carcinoma arising on liver cirrhosis. Abstract 407. European Journal of Cancer 1991; 27Suppl. 2: 72Google Scholar
  77. 77.
    Palmieri G, Gravina A, Topa M, et al. Thymostimulin treatment of hepatocellular carcinoma associated with liver cirrhosis. Report of 31 cases. Gastroenterology 1993a; 104 Suppl.: A438Google Scholar
  78. 78.
    Palmieri G, Gravina A, Topa M, et.al. Long survival of 2 patients with hepatocellular carcinoma on liver cirrhosis treated by thymostimulin. Gastroenterology 1993b; 104 Suppl.: A438Google Scholar
  79. 79.
    Beall G, Kruger S, Morales F, et al. A double-blind, placebo-controlled trial of thymostimulin in symptomatic HIV-infected patients. AIDS 1990; 4: 679–681PubMedCrossRefGoogle Scholar
  80. 80.
    Palmisano L, Biglino A, Panichi G, et al. Combined chemo-immunotherapy (AZT-thymostimulin) in HIV positive patients. A multicenter, randomised, controlled study. Proceedings of the IXth International Conference on AIDS; 1993 Jun 7–11 BerlinGoogle Scholar
  81. 81.
    Chachoua A, Freen MD, Valentine F, et al. Phase I/II trial of thymostimulin in opportunistic infections of the acquired immune deficiency syndrome. Cancer Invest 1990; 7: 225–229CrossRefGoogle Scholar
  82. 82.
    Barbara G, Murri G, Profenna LM, et al. Role of thymostimulin in the treatment of acute Cryptosporidium enteritis with erythromycin in patients with acquired immunodeficiency syndrome. Curr Ther Res 1990; 48: 974–979Google Scholar
  83. 83.
    Barbara G. Acyclovir vs thymostimulin-acyclovir association in the treatment of varicella-zoster virus infection in HIV positive patients. Mediterr J Infect Parasit Dis 1993; 8: 27–30Google Scholar
  84. 84.
    Fagiolo U, Antonini FM, Azzini C, et al. Effetto della timistimolina negli anziani con infezioni respiratorie ricorrenti: risultati clinici ed immunologici di una multi-centrica nazionale. Gior Geront 1992; 40: 105–110Google Scholar
  85. 85.
    Casale G, Zurita IE, Colombo M, et al. Urinary tract infections in the aged: improvement with thymostimulin. Arzneimittel-Forschung 1983; 33: 889–890PubMedGoogle Scholar
  86. 86.
    De Mattia D, Decandia P, Pace D, et al. Effetti immuno-modulanti di un estratto timico (timostimolina) in bambini con infezioni respiratorie ricorrenti [abstract no. 87]. Riv Ital Pediatr 1991; 17Suppl. 4Google Scholar
  87. 87.
    Aiuti F, Sirianni MC, Paganelli R, et al. A placebo-controlled trial of thymic hormone treatment of recurrent herpes simplex labialis infection in immunodeficient hosts. Int J Clin Pharmacol Ther Toxicol 1983; 21: 81–86PubMedGoogle Scholar
  88. 88.
    Aiuti F, Sirianni MC, Fiorilli M, et al. A placebo-controlled trial of thymic hormone treatment of recurrent herpes simplex labialis infection in immunodeficient hosts: results after a 1-year follow-up. Clin Immunol Immunopath 1984; 30: 11–18CrossRefGoogle Scholar
  89. 89.
    Pivetti-Pezzi P, De Liso P, Tamburi S, et al. Thymic factor therapy for herpetic keratitis. Ann Ophthalmol 1985; 17: 327–331PubMedGoogle Scholar
  90. 90.
    Donati L, Periti P. Antibiotic treatment of burned patients: an Italian multicentre study. Intensive Care Med. In pressGoogle Scholar
  91. 91.
    Schiavon M, Chiarelli A, Löhr G, et al. Thymostimulin in the antiinfectious treatment in patients with burns. Arzneimittel-Forschung 1987; 37: 557–560PubMedGoogle Scholar
  92. 92.
    Pernice VW, Schneider H, Wais U, et al. Verbesserte immunkompetenz bei zwei Kindern mit chronischer Epstein-Barr-Virusinfektion inter der Behandlung mit einem standardisierten Thymushormon-Präparat (Thymostimulin). Arzneimittel-Forschung 1985; 35: 869–870PubMedGoogle Scholar
  93. 93.
    Blaim A, Kulesza B, Jackowska T, et al. Thymostimulin in the treatment of chronic candidiasis in children. Mater Med Pol 1985; 2: 111–114Google Scholar
  94. 94.
    Tovo PA, Pugliese A, Palomba E, et al. Thymostimulin therapy n patients with measles meningoencephalitis. Thymus 1986; 8: 91–94PubMedGoogle Scholar
  95. 95.
    Businco L, Rossi P, Quinti I, et al. Therapy with TP-1 of viral diseases in immunodeficient patients. In: Aiuti F, Wigzell H, editors. Thymus, thymic hormones and T lymphocytes. London: Academic Press, 1980: 295–305Google Scholar
  96. 96.
    Muñoz-López F, Martín Mateos MA. Treatment of severe atopic eczema with thymostimulin [abstract no. P221]. Clin Exp Allergy 1990; 20Suppl. 1: 85Google Scholar
  97. 97.
    Harper JI, Mason UA, White TR, et al. A double-blind placebo-controlled study of thymostimulin (TP-1) for the treatment of atopic eczema. Br J Dermatol 1991; 125: 368–372PubMedCrossRefGoogle Scholar
  98. 98.
    Moncada E, Subirá ML, Oleaga A, et al. Insulin requirements and residual beta-cell function 12 months after concluding immunotherapy in Type 1 diabetic patients treated with combined azathioprine and thymostimulin administration for one year. J Autoimmun 1990; 3: 625–638PubMedCrossRefGoogle Scholar
  99. 99.
    Lin C-Y, Lo S. Treatment of hepatitis B virus-associated membranous nephropathy with adenine arabinoside and thymic extract. Kidney Int 1991; 39: 301–306PubMedCrossRefGoogle Scholar
  100. 100.
    Romeo F, Palmisano L, Arcoria D. Thymostimulin in the treatment of hepatitis B surface antigen-positive chronic active hepatitis. Arzneimittel-Forschung 1987; 37: 450–456PubMedGoogle Scholar
  101. 101.
    Sapio C, Bonifati A, Confessore A, et al. Primary prevention: HBV vaccination in hemodialysis unit. Nephron 1992; 61: 360–361PubMedCrossRefGoogle Scholar
  102. 102.
    Aiuti F, Businco L, Ammirati P, et al. Recent advances in therapy of immunodeficiencies. In: Ghia OP, editor. New developments in pediatric research 1977; 2, 557–560Google Scholar
  103. 103.
    Aiuti F, Ammirati P, Fiorilli M, et al. Immunologic and clinical investigation on a bovine thymic extract. Therapeutic applications in primary immunodeficiencies. Pediatr Res 1979; 13: 797–802PubMedCrossRefGoogle Scholar
  104. 104.
    Davies EG, Levinsky RJ. Treatment of cell-mediated immunodeficiency with calf thymic hormone (T.P.I.). Pediatr Res 1982; 16: 573–578PubMedCrossRefGoogle Scholar
  105. 105.
    Lin C-Y, Hsu H-C, Hsieh H-C. Treatment of progressive Bacillus Calmette-Guérin infection in an immunodeficient infant with a specific bovine thymic extract (thymostimulin). Pediatr Infect Dis 1985; 4: 402–405PubMedCrossRefGoogle Scholar
  106. 106.
    Lin C-Y, Hsu C-H, Liu K-C, et al. Serial immunologic and histopathologic studies in the treatment of necrotizing fasciitis with combined immunodeficiency by a bovine thymic extract (thymostimulin). J Pediatr Surg 1986; 21: 1000–1004PubMedCrossRefGoogle Scholar
  107. 107.
    Lin C-Y, Hsu H-C, Chen C-L, et al. Treatment of combined immunodeficiency with thymic extract (thymostimulin). Ann Allergy 1987; 58: 379–384PubMedGoogle Scholar
  108. 108.
    Cacciola E, Guglialmo P, Giustolisi R, et al. Thymostimulin in aplastic anaemia and idiopathic thrombocytopenia. In: Miescher et al. editors. Immunopharmacology. New York: Raven Press, 1985: 193–197Google Scholar
  109. 109.
    Guglielmo P, Giustolisi R, Cacciola E, et al. Immunomodulating treatment in patients with aplastic anemia. N Engl J Med 1983; 308: 1362–1363PubMedGoogle Scholar
  110. 110.
    Tortorella C, Ottolenghi A, Moretti AM, et al. Thymostimulin administration modulates polymorph metabolic pathway in patients with chronic obstructive pulmonary disease. Immunopharmacol Immunotoxicol 1992; 14: 421–437PubMedCrossRefGoogle Scholar
  111. 111.
    Riccio A, Minerva A, Oriente P, et al. Treatment of rheumatoid arthritis with thymostimulin. Clin Tri J 1984; 21: 30–39Google Scholar
  112. 112.
    Touraine J-L. Thymic factor (TP-1) treatment in Di George syndrome. In: Nagel et al. editors. Thymus hormones in oncology. 1988; 19: 79–91Google Scholar
  113. 113.
    Marcos C, Quirce S, Compaired JA, et al. Severe anaphylactic reaction to thymostimulin. Allergy 1991; 46: 235–237PubMedCrossRefGoogle Scholar
  114. 114.
    Bystroň J, Machácek P, Petrek M. Treatment of mild forms of secondary T cell immunodeficiencies by repeated low doses of thymostimulin/TP-1/Serono [abstract no. 1489]. Allergy 1993; 16: 91Google Scholar
  115. 115.
    Sortini A, Navarra G, Donini A, et al. Supporto immunoterapico in chirurgia oncologica. J Emer Surg Intensive Care 1993; 16: 22–32Google Scholar
  116. 116.
    Fiorilli M, Ammirati P, Sirianni MC, et al. Present knowledge of the thymic hormones with particular reference to thymostimulin. In: Aiuti F, Wigzell H, editors. Thymus, thymic hormones and T lymphocytes. London: Academic Press, 1980: 323–337Google Scholar
  117. 117.
    Serono Pharma S.p.A. Thymostimulin prescribing information, Milan, Italy, 1993Google Scholar

Copyright information

© Adis International Limited 1994

Authors and Affiliations

  • Kerry L. Dechant
    • 1
  • Harriet M. Bryson
    • 1
  1. 1.Adis International LimitedMairangi Bay, Auckland 10New Zealand

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