title: IL-10 is critically involved in mycobacterial HSP70 induced suppression of proteoglycan-induced arthritis.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Infectious Diseases and Immunology, Division of Immunology, Utrecht University, Utrecht, the Netherlands.
authors.forename: Lotte
authors.initials: L
authors.lastname: Wieten
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Berlo
authors.forename: Corlinda B
authors.initials: CB
authors.lastname: Ten Brink
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van Kooten
authors.forename: Mahavir
authors.initials: M
authors.lastname: Singh
authors.forename: Ruurd
authors.initials: R
authors.lastname: van der Zee
authors.forename: Tibor T
authors.initials: TT
authors.lastname: Glant
authors.forename: Femke
authors.initials: F
authors.lastname: Broere
authors.forename: Willem
authors.initials: W
authors.lastname: van Eden
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D018840:HSP70 Heat-Shock Proteins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D007114:Immunization; D007249:Inflammation / Q000188:drug therapy; D016753:Interleukin-10 / Q000502:physiology*; D051379:Mice; D009159:Mycobacteriaceae / Q000737:chemistry; D011509:Proteoglycans / Q000009:adverse effects; D012333:RNA, Messenger; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018840:HSP70 Heat-Shock Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D016753:Interleukin-10