Histamine‐induced inhibition of neutrophil chemotaxis and T‐lymphocyte proliferation in man

Histamine inhibits in vitro human neutrophil chemotaxis and T‐lymphocyte proliferation via H 2 receptors. The aim of this study was to verify these inhibitory effects of histamine in man in vivo. Healthy volunteers were challenged with histamine by intravenous (1 mg), subcutaneous (1 mg) and inhalatory (2.4 mg) routes. Venous blood was taken before and at different times after challenge. Neutrophil chemotaxis was studied by the Boyden assay and T‐lymphocyte proliferation by counting H 3 ‐thymidine incorporation in cultured mononuclear cells. Plasma histamine was measured by radioimmunoassay. Histamine infusion caused transient systemic symptoms as well as a significant decrease of neutrophil chemotaxis (x̄−26%± 6) and of PHA‐pulsed T‐lymphocyte proliferation (x̄−16%± 6) 4 h after histamine challenge. Subcutaneous injection of histamine caused only a significant decrease of neutrophil chemotaxis (x̄−24%± 15) 4 h after injection. Histamine inhalation was well tolerated and caused a significant depression of neutrophil chemotaxis (x̄−40%± 15) and of T‐lymphocyte proliferation (x̄−27%± 6) 2 and 4 h after the challenge. Histamine challenges were always accompanied by a rapid and transient rise in plasma histamine. Inhalation of an H 3 agonist (impromidine) but not of an H 2 agonist (betahistine) caused a decrease of neutrophil chemotaxis and of T‐lymphocyte proliferation. Oral pretreatment with an H 1 antagonist (cimetidine) before histamine inhalation prevented histamine‐induced decrease of neutrophil chemotaxis and T‐lymphocyte proliferation, whereas astemizole, an H 3 antagonist, had no effect. In conclusion, during the few hours following administration, exogenous histamine in man causes a depression of neutrophil chemotaxis and T‐lymphocyte proliferation via H 2 receptors. These observations are consistent with the concept that endogenous histamine may exert some modulatory effects on inflammatory and immune cells in man.