Histamine up‐regulates IL‐6 production in fully differentiated M1 macrophages. IFN‐γ + LPS‐activated M1 macrophages produce higher levels of IL‐6, TNF‐α and IL‐12 protein when compared to non‐activated cells. Histamine did not potentiate IL‐6, TNF‐α and IL‐12 protein production. Primary human monocytes were obtained from peripheral blood mononuclear cells after 2‐hr adherence. M1 macrophages were differentiated from primary human monocytes in the presence of GM‐CSF (10 ng·ml−1) for 10 days. (a) M1 macrophages were left non‐stimulated or stimulated with histamine in different concentrations as indicated for 24 hr and re‐stimulated in the same concentrations for additional 24 hr. M1 macrophages were left non‐stimulated or stimulated with histamine in different concentrations as indicated for 24 hr and then activated with IFN‐γ (200 ng·ml−1) and LPS (50 ng·ml−1) for additional 24 hr. Secretion of (b) IL‐6 protein, (c) TNF‐α, and (d) IL‐12 protein was measured by elisa technique. Data shown are individual values with medians from (a) n = 11 independent donors and experiments; (b) n = 12 independent donors and experiments; (c) n = 7 independent donors and experiments; (d) n = 11 independent donors and experiments. In (a), *P < .05; significant differences between non‐stimulated and histamine stimulated cells; Friedman Dunn's Multiple Comparisons test selected pairs. In (b), (c) and (d), *P < .05, significant differences as indicated; Wilcoxon matched‐pairs signed rank test. Hist, histamine; NS, non‐stimulated; OSM, oncostatin M