Histamine enhances granulocyte-macrophage colony-stimulating factor and interleukin-6 production by human peripheral blood mononuclear cells

The effect of histamine on the production of cytokines by subpopulations of mononuclear cells was studied. A 3.5-fold increase in the number of myeloid colony-forming units (CFU-C) was observed when bone marrow cells were cultured in the pres- ence of conditioned medium prepared from nonad- herent mononuclear cells cultured with 1 OM histamine (CM-histamine) compared with phosphate- buffered saline (CM-PBS). Using ELISA and radioim- munoassay kits, histamine was found to enhance the production of GM-CSF (9.6-fold) and IL-6 (8.2-fold) by mononuclear cells but not by nonadherent cells or large granular lymphocytes. Anti-GM-CSF and anti- IL-6 antibodies markedly blocked cytokine activity in CM-PBS, whereas the blocking effect in CM-hista- mine was moderate, indicating enhanced GM-CSF and IL-6 activity in CM-histamine. No GM-CSF or IL-6 levels could be detected in CM-histamine or CM-PBS prepared from CD3�, CD4�, or CD8� lymphocytes. Preincubation of CM-histamine with H1 and H2 re- ceptor antagonists resulted in complete blocking of the histamine-enhanced colony-stimulating activity. We conclude that histamine is able to activate human mononuclear cells to generate cytokines such as GM- CSF and IL-6 via H1 and H2 receptors. J. Leukoc. Biol. 58: 445-450; 1995.