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-α) and chemokines monocyte chemoattractant protein 1 in the joints of arthritic mice or in synovial cell culture supernatant, and increased the levels of IFN-γ and TGF-β. T cells from CCK-8 treated mice proliferated much less, produced low level of IL-17 and high levels of IFN-γ and TGF-β. 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.
Li
Qiaoxia
Q
Institute of Basic Medicine, Hebei Medical University, Zhongshan East Road 361, Shijiazhuang, 050017, Hebei, People's Republic of China.
Cong
Bin
B
Shan
Baoen
B
Zhang
Jingge
J
Chen
Haiying
H
Wang
Tao
T
Ma
Chunling
C
Qin
Jin
J
Wen
Di
D
Yu
Feng
F
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015994:Incidence; D018836:Inflammation Mediators / Q000502:physiology*; D051379:Mice; D008811:Mice, Inbred DBA; D012720:Severity of Illness Index; D012844:Sincalide / Q000502:physiology*; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D012844:Sincalide