Modulation of the adoptive immune response in mice by histamine

The immunodulatory actions of histamine in mice were examined by a combinedin vitro/in vivo approach.Spleen cells from mice were incubated between 2 and 24 hours with histamine (10^–12–10^–3M) under conditions which prevent a change of the free histamine concentration. The cells were subsequently transferred to sublethally irradiated syngenic mice in order to measure the adoptive IgM response. Only stimulatory effects of histamine were found at NMRI mice. However, both stimulatory and inhibitory actions were observed at different histamine concentrations if mice of the strains AB or XVII were used. The graft versus host reaction was measured after transfer of histamine treated spleen cells (strain XVII) to neonatal F₁ (XVII×B10.LP) hybrid mice and revealed both suppressive and stimulatory effects of histamine at different concentrations. A maximal expression of the immunomodulatory effects of histamine was found after 8 hours of preincubation with the donor cells. The action of selective histamine antagonists and cell separation experiments indicated that the effect of histamine on the adoptive IgM response was mediated by H₂-receptors on spleen T-cells. Summarizing, the results indicate that low histamine concentrations elicit bidirectional immunodulatory effects in mice which vary considerably among different strains.