ATTENUATION OF COLLAGEN-INDUCED ARTHRITIS IN MICE BY TREATMENT WITH VECTOR CELLS ENGINEERED TO SECRETE INTERLEUKIN-13

The anti-inflammatory effects of the recently identified cytokine inte rleukin (IL)-13 on collagen-induced arthritis (CIA) was explored and c ompared to those of IL-4 using systemic administration of these cytoki nes via two injections of xenogeneic vector cells transfected with a p lasmid construct. CIA was induced in DBA/1 mice by immunization with n ative bovine type II collagen (CII). Chinese hamster ovary (CHO) fibro blasts transfected with the mouse IL-13 or IL-4 genes were inoculated subcutaneously on days 10 and 25 post-priming with CII and mice were m onitored for signs of arthritis by observers unaware of the status of the animals. Incidence and severity of CIA were significantly reduced in the groups of mice treated with IL-13 and IL-4 gene-transfected CHO cells compared to control groups receiving nontransfected cells. Expr ession of various cytokines in spleen cells from individual mice was a ssessed by quantitative reverse transcriptase-polymerase chain reactio n at different times after immunization. Our data show that IL-13-indu ced suppression of CIA coincided with a decreased TNF-alpha mRNA expre ssion in the spleen of treated animals. This may explain at least part ially the anti-inflammatory effects of IL-13 in CIA. Thus, our results may have important implications for the clinical use of T helper (Th) 1/Th2 modulatory cytokines as therapeutic agents in the treatment of a utoimmune diseases.