IMMUNOMODULATORY EFFECT OF LEVAMISOLE ON RELEASE OF TNF-ALPHA, IL-1-ALPHA, IL-1-BETA AND INTERFERON-GAMMA

Levamisole, an anthelminthic drug, has already been demonstrated to st imulate T-cells and macrophages. In this study whole blood samples of 14 healthy references and 11 patients with nonhematologic tumors prior to therapy were incubated for 6 days at 37 degrees C in 5% CO2. Lipop olysaccharides (LPS) and phytohemagglutinine (PHA), each at a concentr ation of 5 mu g/ml, were used as stimulants. Release of IL-1-alpha, IL -1-beta, TNF-alpha, and Interferon-gamma (IFN-gamma) was assessed in t he supernatants using ELISAs. Results without addition of Levamisole: Unstimulated controls without mitogen showed no measurable IFN-gamma, whereas low concentrations of TNF-alpha, IL-1-alpha and IL-1-beta coul d be found. After stimulation with LPS IL-1-beta increased in both gro ups but significantly lower in tumor patients. PHA induced IFN-gamma s howed an identical reaction. Incubation with Levamisole alone at doses of 1, 5, 10 and 100 mu g/mL. revealed no modulatory effect on IFN-gam ma release compared to controls in both groups. Results under addition of Levamisole: In references Levamisole alone showed no effect on TNF -alpha, IL-1-alpha and also IL-1-beta except for a significant decreas e at 100 mu g/mL. However, in patients IL-1-alpha decreased significan tly at any concentration administered, whereas IL-1-beta significantly increased. TNF-alpha was significantly decreased at 100 mu g/mL in bo th groups. Results under addition of Levamisole and LPS/PHA: In patien ts PHA induced IFN-gamma synthesis did not change significantly in com bination with Levamisole. In references the coincubation with 10 mu g/ mL Levamisole resulted in a significant increase. Costimulation with L PS showed no changes of TNF-alpha in the reference group whereas a sig nificant decrease at each Levamisole concentration in tumor patients w as observed. IL-1-alpha increased significantly in references (1, 5, 1 0 mu g/mL) and in patients (5, 10 mu g/mL). Results for IL-1-beta were comparable with significantly increased values under Levamisole coinc ubation in references (1,5, 10 mu g/mL) and patients (10 mu g/mL). At 100 mu g/mL references showed a significant decrease, not being observ ed in patients. The results may suggest a primary influence of Levamis ole on the release of ''monokines'' such as TNF and especially on IL-1 . The ''lymphokine'' INF-gamma, primarily deriving from CD4+ T-cells, experiences only a marginal influence through Levamisole and then mere ly in reference persons.