From: Cytokines in the pathogenesis of rheumatoid arthritis: new players and therapeutic targets
Experimental arthritis | Rheumatoid arthritis | ||||
---|---|---|---|---|---|
serum | plasma | SF | ST | ||
IL-12 family | |||||
IL-27 |
IL-27Rα KO mice develop more severe CIA [21] IL-27 triggers PGIA [22] IL-27 administration ameliorates CIA and AIA [23,24,25, 27] |
↑ vs HD [28] ↑ in RA-ILD [28] |
↑ vs HD [29] = vs HD and OA [30] | ↑ vs OA [30] | ↑ vs OA [30] |
IL-35 | IL-35 ameliorates CIA [110,111,112] |
↑ in early RA vs established RA [113] ↓ following DMARD therapy ↓ vs HD [115] Inverse correlation with disease activity [115] | na | ↑ vs OA [113] | ↑ vs OA and PsA[114] |
IL-1 family | |||||
IL-33 |
Development and severity of CIA in IL-33 KO mice is comparable to that of WT mice [67] Mice lacking ST2 develop attenuated CIA and AIA [68, 69] Treatment of WT mice with recombinant (r) IL-33 significantly exacerbated CIA and AIA[68, 69] |
↑ vs HD, OA and PsA [70,71,72,73] ↑ in RA-ILD [71] ↑ in erosive RA [71] Lower baseline levels predict good response to anti-TNF-α agents [74, 75] Detectable levels at baseline predict response to RTX [77] Detectable levels at baseline predict atherosclerotic plaque progression [76] | na |
↑ vs OA [26] = vs OA [72] Lower baseline levels predict good response to anti-TNF-α agents [74, 75] | |
IL-36 |
IL-36 is upregulated in CIA, CAIA and AIA [122, 123] IL-36 blockade does not affect arthritis [122, 123] | ↑ vs HD [133] | na | ↑ vs OA [126] | |
IL-37 | Systemic and intra-articular administration of recombinant IL-37 inhibits the development of synovitis in CIA and AIA [146, 147] | ↑ vs HD [133] |
↑ vs HD and OA [147,148,149,150] ↑ in FR+ and anti-CCP+ patients vs seronegative [150] ↑ in active vs inactive RA [149] ↑ in erosive RA [150] | ↑ [150] | ↑ [147] |
IL-38 |
IL-38 KO mice display more severe AIA [131] IL-38 overexpression attenuates CIA and STIA [132] |
= vs HD and OA [131] ↑ vs HD [133] | na | ↑ vs OA [131] | |
Other | |||||
IL-32 | IL-32 administration worsens CIA [44] | ↑ vs HD and OA [46, 47] | na | ↑ vs OA [48, 49] | |
IL-34 |
IL-34 KO mice do not display any autoimmune manifestations [87, 88] CSF-1R blockade is associated with less severe mBSA-IA and CIA [93,94,95] |
↑ vs HD, OA, PsA, AS [96,97,98,99,100] Levels correlate with RF, anti-CCP, ESR, CRP, disease activity, smoking [96,97,98,99] Baseline levels predict radiographic progression [97, 99] | na |
↑ vs HD, OA, PsA, AS [96, 100] Levels are directly correlated with those of SF RANK-L |
↑ [95, 101, 102] Expression associated with the severity of synovitis [95, 101, 102] |