Suppression of streptococcal cell wall-induced arthritis by human chorionic gonadotropin

Objective. To determine whether human chorionic gonadotropin (HCG) contribu tes to pregnancy-associated immunosuppression, as observed clinically by an amelioration of symptoms in human autoimmune diseases, including rheumatoi d arthritis, during pregnancy. Methods. Administration of HCG was initiated 2 days prior to an arthritogen ic dose of streptococcal cell wall (SCW) in nonpregnant female rats, and th e development and severity of SCW-induced arthritis was monitored. Inflamma tory mediators, including plasma nitrite/nitrate and cytokine levels, were measured. Inducible nitric oxide synthase (iNOS) protein and cytokine messe nger RNA expression in joint tissue were compared between treated and untre ated arthritic animals. Results. Systemic administration of HCG resulted in a dose-dependent reduct ion in the clinical arthritis index. Consistent with the amelioration of cl inical symptoms, HCG significantly reduced the inflammatory cell infiltrati on, pannus formation, and bone and cartilage degradation. Mechanistically, HCG therapy was associated with suppression of the overzealous production o f tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-1 beta, which c ontribute to synovial pathology in animals with SCW-induced arthritis. Circ ulating nitric oxide and the amount of iNOS protein were also reduced. Furt hermore, circulating transforming growth factor beta levels were elevated b y the HCG, all of which suggest monocytes/macrophages as a potential target . Conclusion. These findings indicate that HCG exerts a protective effect in this experimental arthritis model, through modulation of inflammatory media tors.