Influence of Arecoline on Immune System: III. Suppression of B Cell-Mediated Immune Response in Mice After Short-Term Exposure

Abstract

Arecoline, a major alkaloid of arecanut was examined to explore its modulatory influence on B cell-mediated immune response in a murine model system. The in vivo and in vitro effects were evaluated at sub-toxic concentrations of arecoline. The number of primary antibody forming cells (AFC) and hemagglutinating and hemolysis antibody titers to Sheep Red Blood Cells (SRBC) were evaluated in male mice. Arecoline exposure for a week invoked dose-dependent effect on primary antibody forming cells to SRBC with a maximum reduction at the dosage of 20 mg/kg bw, a moderate reduction at 10 mg/kg bw and no effect at 5 mg/kg bw dose level. HA and HL antibody titers to SRBC were suppressed markedly at arecoline dosage of 20 mg/kg bw and moderately at a dose of 10 mg/kg bw, given daily for 1, 2 or 3 weeks. The inhibitory effect of arecoline was not dependent on the duration of treatment. Like the primary antibody response, the secondary HA and HL antibody titers were also decreased after arecoline exposure. The administration of arecoline dosages 10 and 20 mg/kg bw daily for 4 days following SRBC immunization also, exerted dose-dependent suppression of primary antibody response. Similarly, when treated after 12 h following immunization, significant reduction in response was observed with arecoline dosage of 20 mg/kg bw. While moderate suppression of antibody response was noticed at the dose level of 10 mg/kg bw, there was no alteration in response at a dosage of 5 mg/kg bw. In contrast, arecoline dosages 5, 10 or 20 mg/kg bw given after 1, 2 or 4 days following immunization did not alter the HA and HL antibody titers to SRBC. Recovery experiments in mice revealed that arecoline-mediated suppression of antibody response is of a reversible nature. Concomitant exposure of arecoline at the concentrations of 10⁻⁵ – 10⁻⁴ M with PWM suppressed ³H-thymidine incorporation of splenic cells in vitro. Taken together, the findings reported in this paper suggest that the intensity of arecoline-mediated suppression of antibody response to SRBC and PWM-induced splenic cell proliferation is dependent upon the dosage and the mode of treatment.