Suppression of IFN-γ Production in Murine Splenocytes by Histamine Receptor Antagonists

Abstract

Accumulating evidence suggests that histamine synthesis induced in several types of tumor tissues modulates tumor immunity. We found that a transient histamine synthesis was induced in CD11b+Gr-1+ splenocytes derived from BALB/c mice transplanted with a syngeneic colon carcinoma, CT-26, when they were co-cultured with CT-26 cells. Significant levels of IFN-γ were produced under this co-culture condition. We explored the modulatory roles of histamine on IFN-γ production and found that several histamine receptor antagonists, such as pyrilamine, diphenhydramine, JNJ7777120, and thioperamide, could significantly suppress IFN-γ production. However, suppression of IFN-γ production by these antagonists was also found when splenocytes were derived from the Hdc−/− BALB/c mice. Suppressive effects of these antagonists were found on IFN-γ production induced by concanavalin A or the combination of an anti-CD3 antibody and an anti-CD28 antibody in a histamine-independent manner. Murine splenocytes were found to express H1 and H2 receptors, but not H3 and H4 receptors. IFN-γ production in the Hh1r−/− splenocytes induced by the combination of an anti-CD3 antibody and an anti-CD28 antibody was significantly suppressed by these antagonists. These findings suggest that pyrilamine, diphenhydramine, JNJ7777120, and thioperamide can suppress IFN-γ production in activated splenocytes in a histamine-independent manner.

Differences of gut microbiota and behavioral symptoms between two subgroups of autistic children based on γδT cells-derived IFN-γ Levels: A preliminary study

“…Altered expression of histamine signaling genes has been found in ASD populations ( 132 ), and antagonism of histamine receptors could reduce autistic behavioral symptoms in ASD individuals and several relevant animal models ( 132 – 135 ). Moreover, histamine receptor antagonists can suppress IFN-γ production ( 136 ), while IFN-γ can also modulate histamine-induced IL-6 and IL-8 production ( 137 ). Our data suggests the histamine degradation capability in fecal microbiota were much more impaired in children with higher levels of IFN-γ, and the decreased capability of histamine degradation may partly affect the autistic behavioral symptoms in ASD children.…”