| T7 |
34754-36068 |
10376735 |
denotes |
4 showed no suppressive effect on disease activity and joint pathology. Interestingly, combination of low-dose IL-4 and IL-10 appeared to have more potent anti-inflammatory effects, and resulted in protection against cartilage pathology [26]. Systemic treatment of murine CIA with high-dose IL-4 (3 μg/day) during the immunization stage delays onset as well as reduces severity. When IL-4 administration was terminated, however, disease expression and activity rapidly accelerated and was indistinguishable from that in the vehicle-treated control group [34]. Systemic IL-4 treatment of streptococcal cell wall arthritis in rats resulted in suppression of disease activity, and ameliorated the chronic destructive process leading to decreased lesions [33]. This was associated with enhanced levels of IL-1Ra, the natural inhibitor of IL-1, which is in accord with observations in the present study and with studies in humans systemically treated with IL-4 [43]. However, it is not likely that the twofold increment in serum IL-1Ra levels, found after IL-4 exposure, is sufficient to suppress CIA. As previously mentioned, blockade of IL-1 by anti-IL-1 antibodies or very high-dose IL-1Ra completely suppressed CIA and lead to full protection against joint pathology [17 |
