A role for histamine receptors in rheumatoid arthritis

Although neurotransmitters and various chemical mediators play an important role in the pathogenesis of rheumatoid arthritis (RA), precise underlying mechanisms have yet to be determined. Histamine is a classical mediator of inflammation and three types of receptors are known. We investigated the presence and functions of histamine receptors of lymphocytes, bone marrow cells, synovial fibroblasts, and chondrocytes in experimentally-induced arthritis and human RA. The function of H2 receptors in peripheral blood lymphocytes and bone marrow cells were down regulated as measured by increments of intracellular cAMP and IL-6 production. Synovial fibroblasts from RA patients did not respond to H2 agonist to synthesize hyaluronic acid. It is evident that H2 receptors are down-regulated in lymphocytes, bone marrow cells, and synovial fibroblasts. The reduced function of H2 receptors in collagen-induced arthritis was normalized by transfer of the receptor-bearing lymphocytes and bone marrow cells. These data suggest that histamine is involved in the pathogenesis of RA.