IL-10 is critically involved in mycobacterial HSP70 induced suppression of proteoglycan-induced arthritis

• Published in: PloS one Vol. 4; no. 1; p. e4186
• Main Authors: Wieten, Lotte, Berlo, Suzanne E, Ten Brink, Corlinda B, van Kooten, Peter J, Singh, Mahavir, van der Zee, Ruurd, Glant, Tibor T, Broere, Femke, van Eden, Willem
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.01.2009; Public Library of Science (PLoS)
• Subjects: Analysis; Animal models; Animals; Antigens; Arthritis; Arthritis, Experimental - chemically induced; Arthritis, Experimental - drug therapy; Binding sites; Bone surgery; CD25 antigen; CD4 antigen; Cytokines; Endoplasmic reticulum; Fibroblasts; Gene expression; Heat shock proteins; HSP70 Heat-Shock Proteins - administration & dosage; HSP70 Heat-Shock Proteins - immunology; HSP70 Heat-Shock Proteins - therapeutic use; Hsp70 protein; Immunization; Immunoglobulin G; Immunology; Immunology/Autoimmunity; Immunology/Immune Response; Immunology/Immunomodulation; Infectious diseases; Inflammation - drug therapy; Inflammatory diseases; Interferon; Interleukin 10; Interleukin-10 - physiology; Lymphocytes; Lymphocytes T; Mice; Mycobacteriaceae - chemistry; Proteins; Proteoglycans - adverse effects; Regulation; Rheumatoid arthritis; Rheumatology; Rheumatology/Autoimmunity, Autoimmune, and Inflammatory Diseases; Rheumatology/Rheumatoid Arthritis; RNA; RNA, Messenger; Shear stress; T cells; T-Lymphocytes - immunology; Vaccination; γ-Interferon; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0004186

The anti-inflammatory capacity of heat shock proteins (HSP) has been demonstrated in various animal models of inflammatory diseases and in patients. However, the mechanisms underlying this anti-inflammatory capacity are poorly understood. Therefore, the possible protective potential of HSP70 and its mechanisms were studied in proteoglycan (PG) induced arthritis (PGIA), a chronic and relapsing, T cell mediated murine model of arthritis. HSP70 immunization, 10 days prior to disease induction with PG, inhibited arthritis both clinically and histologically. In addition, it significantly reduced PG-specific IgG2a but not IgG1 antibody production. Furthermore, IFN-gamma and IL-10 production upon in vitro restimulation with HSP70 was indicative of the induction of an HSP70-specific T cell response in HSP70 immunized mice. Remarkably, HSP70 treatment also modulated the PG-specific T cell response, as shown by the increased production of IL-10 and IFN-gamma upon in vitro PG restimulation. Moreover, it increased IL-10 mRNA expression in CD4+CD25+ cells. HSP70 vaccination did not suppress arthritis in IL-10(-/-) mice, indicating the crucial role of IL-10 in the protective effect. In conclusion, a single mycobacterial HSP70 immunization can suppress inflammation and tissue damage in PGIA and results in an enhanced regulatory response as shown by the antigen-specific IL-10 production. Moreover, HSP70 induced protection is critically IL-10 dependent.