lipid-a and Arthritis

1. We investigated the role of bacterial lipopolysaccharide (LPS) in the reactivation of autoimmune disease by using collagen-induced arthritis (CIA) in mice in which autoimmunity to the joint cartilage component type II collagen (CII) was involved. 2. CIA was induced by immunization with CII emulsified with complete Freund's adjuvant at the base of the tail (day 0) followed by a booster injection on day 21. Varying doses of LPS from E. coli were i.p. injected on day 50. 3. Arthritis began to develop on day 25 after immunization with CII and reached a peak on day 35. Thereafter, arthritis subsided gradually but moderate joint inflammation was still observed on day 50. An i.p. injection of LPS on day 50 markedly reactivated arthritis on a dose-related fashion. Histologically, on day 55, there were marked oedema of synovium which had proliferated by the day of LPS injection, new formation of fibrin, and intense infiltration of neutrophils accompanied with a large number of mononuclear cells. The reactivation of CIA by LPS was associated with increases in anti-CII IgG and IgG2a antibodies as well as various cytokines including IL-12, IFN-gamma, IL-1beta, and TNF-alpha. LPS from S. enteritidis, S. typhimurium, and K. neumoniae and its component, lipid A from E. coli also reactivated the disease. Polymyxin B sulphate suppressed LPS- or lipid A-induced reactivation of CIA. 4. These results suggest that LPS may play an important role in the reactivation of autoimmune joint inflammatory diseases such as rheumatoid arthritis in humans.

Topics: Animals; Antibodies, Monoclonal; Arthritis; Collagen; Cytokines; Escherichia coli; Immunoglobulin G; Injections, Intraperitoneal; Interferon-gamma; Lipid A; Lipopolysaccharides; Male; Mice; Mice, Inbred DBA; Polymyxin B

Rat ankle joints injected intraarticularly with 5 micrograms of group A streptococcal peptidoglycan-polysaccharide (PG-APS) developed an acute course of arthritis. Recurrence of arthritis was induced in 100% of these joints by intravenous injection of as little as 10 micrograms of Salmonella typhimurium lipopolysaccharide (LPS) 3 wk after intraarticular injection. This reaction was similar in athymic and euthymic rats. Buffalo rats were less susceptible than Lewis or Sprague-Dawley rats. Neisseria gonorrhoeae, Yersinia enterocolitica, and Escherichia coli LPS, and S. typhimurium Re mutant LPS, were also active. Re mutant LPS activity was greatly reduced by mixing with polymyxin B. E. coli lipid A was weakly active. An acute synovitis of much less incidence, severity, and duration was seen in contralateral joints injected initially with saline, and in ankle joints of naive, previously uninjected rats after intravenous LPS injection. The intravenous injection of the muramidase mutanolysin on day 0 or 7 after intraarticular PG-APS injection prevented LPS-induced recurrence of arthritis. These studies suggest that the phlogistic activities of lipid A and peptidoglycan might interact in an inflammatory disease process, and that LPS may play a role in recurrent episodes of rheumatoid arthritis or reactive arthritis.

Topics: Animals; Arthritis; Endopeptidases; Female; Lipid A; Lipopolysaccharides; Peptidoglycan; Polysaccharides, Bacterial; Rats; Rats, Inbred BUF; Rats, Inbred Lew; Recurrence; Species Specificity; Synovitis; T-Lymphocytes