THE IMMUNOMODULATORY EFFECT OF LEVAMISOLE IS INFLUENCED BY POSTOPERATIVE CHANGES AND TYPE OF LYMPHOCYTE STIMULANT

The results of both laboratory and clinical research into the immunomo dulatory activity of levamisole have shown a considerable degree of in consistency and sometimes contradiction. This is probably a reflection of the lack of understanding of the mechanism(s) of action of levamis ole and it is therefore necessary to base conclusions about its immuno modulatory efficacy in the treatment of disease on experimental assays that take into consideration the in vivo conditions. This investigati on was designed to compare the immunomodulatory activity of levamisole under clinically achievable and non-achievable conditions as judged b y changes in the perioperative proliferative response of lymphocytes f rom 30 patients with colorectal cancer. The results obtained showed th at proliferation in antigen (purified protein derivative, PPD)-stimula ted, but not phytohaemagglutinin(PHA)- or staphylococcal-enterotoxin-B (SEB)-stimulated, lymphocyte cultures was consistently and significant ly augmented by levamisole in concentrations of 25 ng-25 mu g/ml. High concentrations of levamisole (25 mu g/ml and 100 mu g/ml) were inhibi tory to PHA- and SEB-stimulated, but not PPD-stimulated, lymphocyte cu ltures, especially in the postoperative period. Of particular interest was the observation that, although levamisole temporarily lost its st imulatory activity in the postoperative period (third postoperative da y), it did enhance antigen-stimulated lymphocytes at the time of the n adir of the postoperative suppression of lymphocyte proliferation (fir st postoperative day). Clinically achievable concentrations of levamis ole are therefore effective both before and after operation in enhanci ng the response of lymphocytes to antigens.