Cimetidine modulates chemiluminescence and superoxide generation by neutrophils

Cimetidine, a known H2 blocker, markedly inhibited the generation of luminol-dependent chemiluminescence (LDCL) and the generation of Superoxide by human neutrophils (PMNs) stimulated by polycation-opsonized streptococci. Cimetidine also inhibited LDCL generation in peritoneal PMNs derived from mice pre-injected with this drug. The elucidation of the mechanisms of LDCL inhibition involved the employment of a variety of cimetidine analogues. The most effective inhibitory activity, besides cimetidine, was displayed by histamine, histidine, imidazole acetate, anserine and ergothionine. Imidazole, carnosine and homocarnosine had no inhibitory effect on oxygen radical generation. The possible mechanisms by which cimetidine and certain of its analogues affect the respiratory burst in leucocytes is discussed.