The immunomodulatory effect of levamisole is influenced by postoperative changes and type of lymphocyte stimulant
- 70 Downloads
The results of both laboratory and clinical research into the immunomodulatory activity of levamisole have shown a considerable degree of inconsistency and sometimes contradiction. This is probably a reflection of the lack of understanding of the mechanism(s) of action of levamisole and it is therefore necessary to base conclusions about its immunomodulatory efficacy in the treatment of disease on experimental assays that take into consideration the in vivo conditions. This investigation was designed to compare the immunomodulatory activity of levamisole under clinically achievable and non-achievable conditions as judged by changes in the perioperative proliferative response of lymphocytes from 30 patients with colorectal cancer. The results obtained showed that proliferation in antigen (purified protein derivative, PPD)-stimulated, but not phytohaemagglutinin(PHA)- or staphylococcal-enterotoxin-B(SEB)-stimulated, lymphocyte cultures was consistently and significantly augmented by levamisole in concentrations of 25 ng–25μg/ml. High concentrations of levamisole (25 μg/ml and 100 μg/ml) were inhibitory to PHA- and SEB-stimulated, but not PPD-stimulated, lymphocyte cultures, especially in the postoperative period. Of particular interest was the observation that, although levamisole temporarily lost its stimulatory activity in the post-operative period (third postoperative day), it did enhance antigen-stimulated lymphocytes at the time of the nadir of the postoperative suppression of lymphocyte proliferation (first postoperative day). Clinically achievable concentrations of levamisole are therefore effective both before and after operation in enhancing the response of lymphocytes to antigens.
Key wordsLevamisole lymphocytes PPD SEB PHA
Unable to display preview. Download preview PDF.
- 1.Amery WK, Christian H (1984) Levamisole. In: Fenichel RL, Chrigos MA (eds) Immune modulation agents and their mechanisms. Dekker, New York, p 383Google Scholar
- 3.Boyum A (1968) Separation of leukocytes from blood and bone marrow. Scand J Clin Lab Invest 21 [Suppl 97]: 1Google Scholar
- 4.Daly LE, Bourke GJ, McGilvrey J (1991) Interpretation and uses of medical statistics, 4th edn. Blackwell Scientific, OxfordGoogle Scholar
- 9.Kimball ES, Schneider CR, Jisher MC, Clark MC (1992) Levamisole causes differential cytokine expression by elicited mouse peritoneal macrophages. J Leukoc Biol 25:349Google Scholar
- 10.Lichtenfeld JL, Desner MR, Wiernik PH, Mardiney MR, Jr (1976) Modulating effects of levamisole (NSC-177023) on human lymphocyte response in vitro. Cancer Treat Rep 6:571Google Scholar
- 13.Miwa H, Kawai T, Nakahara H, Orita K (1980) Decrease in cell mediated immunity by surgical intervention and its prevention by levamisole. Int J Immunopharmacol 2:31Google Scholar
- 16.Renoux G (1980) The general immunopharmacology of levamisole. Drugs 19:89Google Scholar
- 19.Sharon N, Lis H (1989) Lectins. Chapman & Hall, London, p 126Google Scholar
- 21.Symoens J, De Cree J, Van Beoer WFM, Janssen PAJ (1979) Levamisole. In: Goldberg ME (ed.) Pharmacological and biochemical properties of drug substances. American Pharmaceutical Association & Academy of Pharmaceutical Sciences, Washington, p 407Google Scholar