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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.
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.
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.
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.
KeywordsHuman Immunodeficiency Virus Adis International Limited Atopic Eczema Zidovudine Bovine Spongiform Encephalopathy
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- 1.Roitt I. Essential Immunology Seventh Edition. Oxford: Black-well Scientific Publications, 1991Google Scholar
- 2.Skotnicki AB. Thymic hormones and lymphokines. Drugs Today 1989; 25: 337–362Google Scholar
- 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
- 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.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.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
- 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.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.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
- 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
- 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.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
- 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.Surico N, Tavassoli K. Timostimolina nel trattamento della malattia infiammatoria pelvica ricorrente. Immunologica Clinica 1993; 12: 21–31Google Scholar
- 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
- 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
- 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
- 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.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.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
- 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.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
- 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.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.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
- 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
- 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
- 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.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.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.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.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.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.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
- 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.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.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.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
- 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
- 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.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.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
- 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
- 90.Donati L, Periti P. Antibiotic treatment of burned patients: an Italian multicentre study. Intensive Care Med. In pressGoogle Scholar
- 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
- 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.Muñoz-López F, Martín Mateos MA. Treatment of severe atopic eczema with thymostimulin [abstract no. P221]. Clin Exp Allergy 1990; 20Suppl. 1: 85Google Scholar
- 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
- 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
- 111.Riccio A, Minerva A, Oriente P, et al. Treatment of rheumatoid arthritis with thymostimulin. Clin Tri J 1984; 21: 30–39Google Scholar
- 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
- 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.Sortini A, Navarra G, Donini A, et al. Supporto immunoterapico in chirurgia oncologica. J Emer Surg Intensive Care 1993; 16: 22–32Google Scholar
- 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.Serono Pharma S.p.A. Thymostimulin prescribing information, Milan, Italy, 1993Google Scholar