Regulatory role of interleukin 10 in joint inflammation and cartilage destruction in murine streptococcal cell wall (SCW) arthritis. More therapeutic benefit with IL-4/IL-10 combination therapy than with IL-10 treatment alone.
Interleukin 10 (IL-10) and IL-4 are important downregulators of a number of macrophage functions. The authors investigated the role of endogenous IL-4 and IL-10 and the therapeutic effect of addition of these cytokines on joint inflammation and cartilage destruction in the early stages of the macrophage dependent murine streptococcal cell wall (SCW) arthritis model. It was demonstrated that endogenous IL-10, but not IL-4, plays a pivotal role in the regulation of SCW arthritis. Blocking endogenous IL-10 with anti-IL-10 antibodies resulted in a sustained arthritis with more dense synovial infiltrate as well as enhanced cartilage damage. Adding exogenous IL-10 further enlarged the suppressive effect of endogenous IL-10. Even more pronounced amelioration was found with the combination IL-4/IL-10. This resulted in a reduced swelling and a restorative overshoot in chondrocyte proteoglycan synthesis at day 4 (140%). Treatment with the combination IL-4/IL-10 not only a marked reduction of tumour necrosis factor alpha (TNF-alpha) levels, like IL-10 treatment alone, but also the IL-1 beta levels were strongly reduced in the synovium. In conclusion, the data is consistent with a dominant role of IL-10 in natural suppression of arthritis expression, whereas combined treatment with IL-4 and IL-10 appears to be of potential therapeutic value.
Lubberts
E
E
Department of Rheumatology, University Hospital Nijmegen, The Netherlands. E.Lubberts@REUMA.AZN.NL
Joosten
L A
LA
Helsen
M M
MM
van den Berg
W B
WB
D000818:Animals; D001170:Arthritis, Infectious / Q000188:drug therapy / Q000276:immunology*; D002358:Cartilage, Articular / Q000276:immunology* / Q000503:physiopathology; D002473:Cell Wall; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology* / Q000627:therapeutic use; D015847:Interleukin-4 / Q000276:immunology* / Q000627:therapeutic use; D007719:Knee Joint / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013290:Streptococcal Infections / Q000188:drug therapy / Q000276:immunology*; D013291:Streptococcus / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4