Therapeutic effect of low-dose IL-18 combined with IL-10 on collagen-induced arthritis by down-regulation of inflammatory and Th1 responses and induction of Th2 responses.
To investigate the anti-inflammatory or pleiotropic immunomodulatory role of interleukin-18 (IL-18), collagen-induced arthritis (CIA) mice were administrated with IL-18 along or in combination with IL-10, IL-4 or IL-12. IL-18 treatment along had no therapeutic effect on onset or established CIA mice. However, the combined treatment of low-dose IL-18 with IL-10 ameliorated the disease progression. Th1 cytokine expression was significantly inhibited, whereas Th2 cytokine expression was up-regulated in the synovial tissue by the IL-18/IL-10 treatment when compared with that in control group. Interestingly, IL-18 receptor (IL-18R) alpha expression was down-regulated by the treatment. According to the development of Th2 responses, GATA-3 mRNA expression was significantly increased in the treatment group. Our results indicated that combined treatment of low-dose IL-18 with IL-10 can prevent the development of CIA, which may be mediated not only by inhibiting Th1 responses through IL-18/IL-18Ralpha signaling, but also by inducing anti-inflammatory mediators through a GATA-3-dependent mechanism.
Dai
Qiaomei
Q
Department of Rheumatology, The Second Affiliated Hospital of Harbin Medical University, No 246 Xuefu Road, 150081, Harbin, China.
Li
Yang
Y
Zhang
Fengshan
F
Yu
Haiyue
H
Wang
Xiaoyan
X
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D003094:Collagen / Q000276:immunology / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004359:Drug Therapy, Combination; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020382:Interleukin-18 / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
D020382:Interleukin-18; D011994:Recombinant Proteins; D016753:Interleukin-10; D003094:Collagen