Hexachlorobenzene-induced stimulation of the humoral immune response in rats

Rats were fed diets containing 0, 500, 1000, and 2000 mg HCB/kg during a 3-week period. Marked weight increases of spleen, popliteal and mesenteric lymph nodes and of the liver were found. Histologically, the white pulp in the spleen was enlarged because of an increase in size of marginal zones and follicles. In addition, there was an increase of extramedullary hemopoiesis. In the lymph nodes, the number of high endothelial venules was increased at all dose levels. The number of neutrophils, basophils and monocytes in the peripheral blood was significantly increased, whereas peripheral lymphocyte counts were slightly higher. Total serum IgM levels were markedly increased, but IgG concentrations were unaltered. On the basis of this experiment, the 1000 mg HCB/kg diet level was chosen for the different function studies that were carried out after a 3-weeks dietary regimen. Regarding the humoral immunity, IgM antibodies to LPS were unaltered, whereas primary and secondary IgM and IgG antibody titers to tetanus toxoid were increased approximately three-fold. HCB did not significantly alter the cell-mediated immunity, as shown by the following parameters: resistance to Listeria monocytogenes infection, rejection of skin transplants, and delayed-type hypersensitivity to tuberculin. The phagocytizing capacity of macrophages was studied by measuring the blood clearance of carbon particles. HCB did slightly depress the phagocytic index, but the difference with control animals was statistically not significant. The in vitro responsiveness of thymus cells to the mitogens PHA, Con A, and PWM was not changed by in vivo HCB-treatment. On a cell-for-cell basis, the responsiveness of spleen cells was increased when cultured in the presence of LPS. On a whole organ basis, the response to PHA, Con A, PWM, and LPS was markedly enhanced because of an increase in the number of nucleated spleen cells. Regarding peripheral lymphocytes, only the response to the mitogen Con A was higher. On the basis of these studies it is concluded that HCB stimulates the humoral immune response in the rat, enhances the in vitro responsiveness of spleen cells to the different mitogens mainly as a result of an increase in the number of splenic lymphocytes, but does not alter the cell-mediated immunity as shown with in vivo tests. This result contrasts with data in the literature that show that HCB suppresses the humoral and cell-mediated immunity in mice. Finally, HCB pretreatment only marginally increased the susceptibility of rats to endotoxin, whereas mice have been shown to be 20-fold more susceptible to the lethal effects of bacterial endotoxin.