Inhibition of adjuvant arthritis by histamine

Histamine was injected subcutaneously to rats at doses of 2--10 mg/kg, twice daily for various periods after an intradermal adjuvant injection into one hind paw. The administration of histamine prevented the appearance of the secondary lesion in the noninjected paw, but did not affect the primary swelling of the injected paw or the established secondary lesion. The histamine effect was dose-dependent with the most effective time of administration being from the 5th to the 10th day after adjuvant injection. Arthritic lesions found in control animals in histological and roentgenographic examinations were also inhibited in histamine-treated animals. Sinomenine, a histamine releaser, likewise showed a suppressive effect on the secondary lesion. Burimamide, a histamine H2-receptor antagonist, blocked these histamine effects, while mepyramine, a H1-receptor antagonist, did not have such a blocking effect. The findings suggest that histamine may inhibit the development of adjuvant arthritis by an immunosuppressive mechanism mediated through activation of H2-receptors on lymphoid cells.