Cholecystokinin octapeptide exerts its therapeutic effects on collagen-induced arthritis by suppressing both inflammatory and Th17 responses

The purpose of this study was to evaluate the potential therapeutic effect of cholecystokinin octapeptide (CCK-8) on collagen-induced arthritis (CIA), an accepted murine experimental disease model with diverse histopathological features similar to human rheumatoid arthritis (RA). CIA was induced in DBA/1J mice by immunization with chicken collagen type II (CII). CCK-8 at different doses was intraperitoneally administered daily for 1 week. Mice treated with CCK-8 at doses of 5 and 10 nmol but not 1 nmol displayed much delayed onset of CIA and significantly lower incidence and decreased severity of arthritis. CCK-8 treatment significantly reduced the production of cytokines (IL-17, IL-23, IL-6 and TNF-alpha) and chemokines monocyte chemoattractant protein 1 in the joints of arthritic mice or in synovial cell culture supernatant, and increased the levels of IFN-gamma and TGF-beta. T cells from CCK-8 treated mice proliferated much less, produced low level of IL-17 and high levels of IFN-gamma and TGF-beta. Moreover, CCK-8 treated mice showed lower levels of CII-specific IgG, particularly that of IgG2a, in sera than those from control mice. These results indicate that CCK-8 is effective in suppressing both inflammatory and Th17 responses in CIA. CCK-8 may represent a new therapeutic modality for rheumatoid arthritis.