Bacterial lipopolysaccharide acts as an adjuvant to induce autoimmune arthritis in mice.
We investigated the ability of lipopolysaccharide (LPS) as an adjuvant to induce autoimmune arthritis. LPS from Escherichia coli was intraperitoneally injected into DBA/1J mice together with the joint cartilage component type II collagen (CII) on day 0. Thereafter, the injection of CII and LPS was continued every 2 weeks up to day 56. The results showed that mice injected with CII plus LPS had signs of arthritis on day 55 and the joint inflammation reached a peak on day 75. Injection of CII or LPS alone induced no arthritis. Histologically, marked oedema of synovium and intense infiltration of inflammatory cells, including neutrophils, were observed 3 days after the onset of joint inflammation. Twenty-one days later, there were marked proliferation of synovial tissues with many mononuclear cells and destruction of cartilage. Anti-CII immunoglobulin G (IgG) and IgG2a antibodies were markedly produced in mice injected with CII plus LPS. Pronounced secretion of cytokines, including interleukins-12 and -1beta, interferon-gamma and tumour necrosis factor-alpha, was also observed in these animals. Arthritis was passively transferred into naive syngeneic mice with sera but not with lymphoid cells from mice given CII with LPS. Other types of LPS from Salmonella enteritidis, Salmonella typhimurium and Klebsiella pneumoniae as well as lipid A from E. coli, induced inflammation in joints when administered with CII. Polymixin B sulphate mixed with LPS or lipid A blocked the induction of joint inflammation. These results indicate that LPS appears to play an important role as an adjuvant in the induction of arthritis in which autoimmunity to CII is involved.
Yoshino
S
S
Department of Microbiology, Saga Medical School, Saga, Japan.
Sasatomi
E
E
Ohsawa
M
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D019264:Adoptive Transfer; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000097:blood; D001169:Arthritis, Experimental / Q000139:chemically induced* / Q000276:immunology; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000276:immunology; D003094:Collagen / Q000276:immunology* / Q000494:pharmacology; D004926:Escherichia coli; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000032:analysis; D007375:Interleukin-1 / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D007596:Joints / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008198:Lymph Nodes / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000032:analysis; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009504:Neutrophils / Q000276:immunology; D011112:Polymyxin B / Q000494:pharmacology; D013154:Spleen / Q000276:immunology; D013997:Time Factors
D000276:Adjuvants, Immunologic; D000900:Anti-Bacterial Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008233:Lymphotoxin-alpha; C048844:anti-IgG; D018664:Interleukin-12; D007371:Interferon-gamma; D003094:Collagen; D011112:Polymyxin B