The effect of histamine on the development of adjuvant arthritis in the rat.

Histamine, injected subcutaneously (0.3-10 mg/kg), produced a dose-related inhibition of the primary and secondary inflammation, and the development of the secondary lesions of rat adjuvant arthritis. Histamine was effective when given for short periods around the time of adjuvant administration and could also delay and possibly reverse an established arthritic response. The histamine H1-agonist, 2-(2-pyridyl)-ethylamine, inhibited rat adjuvant arthritis, whereas the histamine H2-agonists, impromidine and dimaprit, failed to affect the response. Metiamide, a histamine H2-antagonist (5 mg/kg), reduced the inflammation in the uninjected hind-paw and the development of secondary lesions. Histamine may have two effects on rat adjuvant arthritis, inhibiting the response via stimulation of H1-receptors and augmenting the response via stimulation of H2-receptors. Since histamine is known to bind to and to alter the reactivity of cells which are involved in the regulation of immune responsiveness, it is suggested that interactions with these cells are responsible for the observed effects of histamine.