Influence of Arecoline on Immune System: II. Suppression of Thymus-Dependent Immune Responses and Parameter of Non-specific Resistance After Short-Term Exposure

Abstract

Arecoline, a major alkaloid of arecanut was screened to explore its modulatory influence on cell-mediated immune response in a murine model system. The in vivo and in vitro effects were evaluated at subtoxic concentrations of arecoline. Delayed type hypersensitivity (DTH) reactions to sheep red blood cells (SRBC) were evaluated in male mice. When treated subcutaneously with 20 mg/kg bw (1/5 of LD50) dose of arecoline for 1, 2 or 3 weeks, the DTH reactions were significantly suppressed. At arecoline concentration of 10 mg/kg bw, there was a moderate reduction in DTH response, while no appreciable change was observed at a dosage of 5 mg/kg bw. The effects were not dependent on the duration of treatment. In contrast, treating with arecoline continuously for 4 days following SRBC immunization showed significant suppression in DTH reactions at both 10 and 20 mg/kg bw doses. When treated after 12 h following immunization with 20 mg/kg bw arecoline, significant reduction in DTH reactions were seen. While moderate reduction in response was observed with arecoline dosage of 10 mg/kg bw, there was no alteration in response at the dose level of 5mg/kg bw. Recovery experiments in mice revealed that arecoline mediated effects are of a reversible nature. Arecoline treatment did not appreciably alter the host resistance to endotoxin shock. In vitro experiments revealed both dose-dependent and time-dependent cytotoxic effects of arecoline when spleen cells were incubated with varying concentrations of arecoline. Concomitant exposure of arecoline at concentrations of 10(-6) - 10(-4) M with con A, markedly suppressed both 3H-thymidine incorporation and interleukin-2 production of splenic cells. In contrast, concomitant exposure of arecoline with IL-2 did not alter 3H-thymidine incorporation in the IL-2 dependent cytolytic T-lymphocyte line (CTLL), except at the concentration of 10(-4) M arecoline. From these studies it is concluded that the dose-dependent suppressive effects of arecoline on DTH response to SRBC and on certain in vitro lymphocyte functions are more clear than the host resistance to endotoxin shock.