Clinical Immunotherapeutics

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


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



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.


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.


Human Immunodeficiency Virus Adis International Limited Atopic Eczema Zidovudine Bovine Spongiform Encephalopathy 
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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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