A role for histamine type II (H-2) receptor binding in production of the lymphokine, soluble immune response suppressor (SIRS)

Soluble immune response suppressor (SIRS) is an immunosuppressive protein produced by human and murine suppressor cells activated by a variety of agents. Because histamine has been reported to activate suppressor cells, the possibility that it also induced SIRS production was investigated. Human lymphocytes treated with 10(-4) M histamine for less than 1 hr released a suppressive substance into culture supernatants that was physically, functionally and antigenically similar to human SIRS. Cimetidine and ranitidine, structurally distinct histamine type II (H-2) receptor antagonists, prevented histamine-induced SIRS production. In further experiments, suppression of human polyclonal IgM PFC responses by Con A and interferons, substances that activate the SIRS pathway, was inhibited by H-2 receptor antagonists. Activation of lymphocytes to produce SIRS by Con A or interferons was blocked by cimetidine or ranitidine. These data demonstrate that production of SIRS is induced by histamine, and raise the possibility that H-2 receptor binding may play a role in the SIRS pathway.