Selective, histamine-mediated immunosuppression in laryngeal cancer

Immunosuppression observed even in the earliest laryngeal cancers can be, in part, reversed with H2 histamine antagonists. In an effort to explain this, we tested whether histamine could evoke changes in endogenous antitumor lymphokine production using tonsil lymphocytes as test cells. We have observed that lymphocytes, treated in vitro with histamine, display a significant suppression of lymphokine production and mixed lymphocyte proliferation response following galactose oxidase treatment. Interferon gamma production was reduced to less than 2% of control value in the presence of histamine. In contrast, the lymphokine-activated killer cell activity induced by purified, natural interleukin-2 was not affected by similar concentrations of histamine. Histamine appears to exert its inhibitory effect by stimulating the production of a substance released by suppressor T cells. The suppressive effects observed could be reversed by concomitant or sequential treatment with cimetidine or ranitidine and not by H1 histamine antagonists, indicating that it occurs through an H2 histamine receptor. These experiments suggest that histamine may have a profound suppressive effect on the lymphocyte population studied.