Oral administration of lipopolysaccharide exacerbates collagen-induced arthritis in mice

We investigated whether oral administration of LPS exacerbated collagen-ind uced arthritis (CIA) in mice, which was an experimental model of autoimmune disease. CIA was induced by s.c. injection of type II collagen emulsified with CFA into the base of the tail (day 0) followed by a booster injection on day 21, To examine the ability of LPS to exacerbate CIA, varying doses o f LPS were orally administered on day 50, The results showed that administr ation of LPS was followed by reactivation of CIA in a dose-related fashion. Histologically, on day 55 there were marked edema of synovium proliferated by day 50, new formation of fibrin, and intense infiltration of neutrophil s accompanied with a large number of mononuclear cells. Severe destruction of cartilage and subchondral bone was also observed on day 70, The reactiva tion of CIA by oral administration of LPS was associated with increase in a nti-type II collagen IgG and IgG2a Abs as well as varying kinds of cytokine s including IL-12, IFN-gamma, IL-1 beta, and TNF-alpha, Polymyxin B sulfate given either orally or i.v. suppressed the recurrence of CIA. Increased am ounts of LPS were found in sera of mice given the endotoxin orally. LPS fro m Salmonella enteritidis, Salmonella typhimurium, and Klebsiella pneumoniae and its component, lipid A from Escherichia coli, also reactivated the dis ease, These findings suggest that LPS from intestinal bacteria may play a r ole in the exacerbation of autoimmune joint inflammation.