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Table 1 Data on different cytokines in experimental arthritis and patients with rheumatoid arthritis

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]

  1. SF synovial fluid, ST synovial tissue, KO knock-out, WT wild type, CIA collagen induced arthritis, PGIA proteoglycan-induced arthritis, AIA antigen induced arthritis, CAIA collagen antibody-induced arthritis, STIA K/BxN serum transfer-induced arthritis, mBSA methylated bovine serum albumin, HD healthy donors, OA osteoarthritis, PsA psoriatic arthritis, AS ankylosing spondylitis, ILD interstitial lung diseas, TNF, tumour necrosis factor, RTX rituximab, RF rheumatoid factor, anti-CCP anti cyclic cutrullinated peptide, ESR erythrosedimentation rate, CRP C reactive protein, RANK-L receptor activator of nuclear factor κ-B ligand, DMARDs disease modifying anti-rheumatic drugs