Failure of the H2 antagonist cimetidine to reverse parasite antigen-specific lymphocyte unresponsiveness in experimental filariasis

Histamine is known to mediate potent immunosuppressive effects on lymphocyte function. In jirds infected with Brugia pahangi decreased mitogen and parasite antigen responsiveness are associated with the presence of histamine binding regulatory cells. The present study was thus designed to investigate the immunoregulatory role of histamine in experimental filariasis. Spleen cells from normal or B. pahangi infected jirds were incubated with BSA or histamine coupled Sepharose beads and the degree of cell-bead binding was quantitated. Cells from infected jirds demonstrated increased levels of histamine, but not BSA binding relative to normal cells, and this binding was blocked by soluble histamine or by the histamine receptor antagonist cimetidine. Cimetidine failed to restore the in vitro responsiveness of spleen cells from infected jirds to phytohemagglutinin or to a soluble extract of B. pahangi. Cimetidine did, however, reverse histamine-induced suppression of normal spleen cell responses to PHA. The present results suggest that histamine does not play a major role in the immunoregulatory alterations induced by B. pahangi infection.