Effects of prolactin in stimulating disease activity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), a chronic autoimmune illness, is influenced by hormones. High prolactin concentrations were associated with early death from autoimmune renal disease in NZB/NZW mice, an animal model of severe SLE. NZB/NZW mice that delivered and nursed pups and those that underwent pseudopregnancy had changes in serum IgG and autoantibodies. NZB/NZW mice treated with the prolactin-suppressing drug bromocriptine had prolonged lives. Elevated serum prolactin concentrations are reported in SLE patients of both sexes. We found four women with long-standing hyper-prolactinemia who developed SLE. A survey of premenopausal women whose sera were submitted for autoantibody testing showed that 20% with anti-ds-DNA antibodies also had high prolactin levels. Many hyperprolactinemic patients whose sera were referred to an endocrinology laboratory had positive FANA tests (women 33%, men 53%) but did not have SLE. Disease activity was suppressed in six of seven SLE patients treated with bromocriptine. All had elevated disease activity and five became unexpectedly hyperprolactinemic after treatment stopped. Manipulating serum prolactin affords a means of treating clinical SLE activity.

Animal models in rheumatoid arthritis.

Two new models for the study of rheumatoid arthritis have been established. SCID (severe combined immunodeficient) mice implanted with human synovial tissues and human HLA-DR4-CD4 transgenic mice represent novel and important approaches to the use of animal models in pathogenetic studies. New studies of streptococcal cell wall arthritis in rats demonstrated that beta 1 integrin-mediated cell-matrix interactions are involved in the induction and perpetuation of inflammatory synovitis and that systemic administration of interleukin-4 selectively suppresses established synovitis, presumably by effects on monocyte function. The importance of nitric oxide as a mediator of synovial inflammation was confirmed in the adjuvant-induced model of rheumatoid arthritis. In the collagen-induced arthritis model, interesting new data have implicated gamma delta T cells in the pathogenesis of arthritis, and the antineoplastic drug taxol was shown to have anti-inflammatory effects.