Inhibition by glucocorticoids of mitogen-dependent histamine biosynthesis caused by histidine decarboxylase in cultured mouse spleen cells and peritoneal adherent cells.

When spleen cells of C57BL/6 mice were cultured, their histidine decarboxylase (HDC) activity increased with a concomitant increase in the histamine concentration in the culture medium. The addition of concanavalin A (Con A) or E. coli lipopolysaccharide (LPS) to the culture enhanced the responses. Treatment with dexamethasone or corticosterone significantly inhibited both spontaneous and Con A-dependent induction of HDC and histamine biosynthesis. Progesterone and estradiol did not inhibit but rather enhanced the responses. Testosterone had little effect on HDC activity and the histamine level of the culture medium of spleen cells. Adherent cells obtained from glycogen-stimulated peritoneal exudates had the enzyme constitutively. Con A had no appreciable effect on the HDC activity and the histamine level of the culture of these adherent cells. However, the addition of conditioned medium of T + B lymphocytes that had been incubated in the presence of Con A rendered the adherent cells responsive to Con A, leading to an increase in the HDC activity and the histamine level of the culture of the cells. Treatment with dexamethasone largely abrogated the responses. The results suggest that HDC-dependent histamine biosynthesis by peritoneal adherent cells is inhibited by glucocorticoids, which act on the adherent cells per se.