Effect of histamine on delayed-type hypersensitivity in mice.

The effect of histamine on delayed-type hypersensitivity provoked in the abdominal cavity of mice was studied. When histamine (0.1-10 mg/kg) was injected twice a day for 2 consecutive days after antigen challenge, cell accumulation in the inflamed site and the production of lymphokine was significantly suppressed. Similar suppressive effects were observed after injection with an H2-agonist, dimaprit, but not in the case of an H1-agonist, 2-methylhistamine. The effect of histamine on cell accumulation in an implanted sponge was blocked by the H2-antagonists, cimetidine and ranitidine, but only slightly by the H1-antagonists, pyrilamine and diphenhydramine. In adrenalectomized mice, the suppressive effect of histamine was slightly weaker than in normal mice, but the inhibitory effect of histamine was almost completely blocked by H2-antagonists in both cases. The suppressive effect of histamine on the production of lymphokine (macrophage chemotactic factor) was also blocked by cimetidine. Using gel chromatography, the chemotactic activity fraction was eluted as molecules having a molecular weight of 30,000-70,000. These results suggest that the histamine-induced suppression of the delayed-type hypersensitivity reaction in mice is affected mainly by the production of lymphokine(s) via an H2-receptor-bearing lymphocyte.