IL-10 is critically involved in mycobacterial HSP70 induced suppression of proteoglycan-induced arthritis.
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.
Wieten
Lotte
L
Institute of Infectious Diseases and Immunology, Division of Immunology, Utrecht University, Utrecht, the Netherlands.
Berlo
Suzanne E
SE
Ten Brink
Corlinda B
CB
van Kooten
Peter J
PJ
Singh
Mahavir
M
van der Zee
Ruurd
R
Glant
Tibor T
TT
Broere
Femke
F
van Eden
Willem
W
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
D018840:HSP70 Heat-Shock Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D016753:Interleukin-10