|
| Cytokines/blockade | Human RA or mouse model | Expression | Migration or recruitment | Apoptosis or survival | NET formation | Outcome |
|
| TNF-α | Human RA | ↑ in serum and synovial fluid [13, 18, 19] | ↑ in vitro [11] | Promote or delayed apoptosis In vitro [27] | ↑ in vitro [13] | |
| Blockade of TNF-α | Human RA | — | ↓in vivo [18] | Antiapoptotic Mcl-1 ↑ and proapoptotic caspase-9 ↓ [57] | ↓ in vitro [13, 73] | Improved [73, 98] |
| TNFR−/− | Collagen Ab and LPS-inducedarthritis model | — | ↓ in vivo [52] | — | — | Improved [52] |
| IL-6 | Human RA | ↑ in serum and synovial fluid [19–21] | No effect in vitro [21] | No effect in vitro [21], delayed apoptosis in vitro [27] | ↑ in vitro [73] ↑ in vitro [75] | — |
| Blockade of IL-6 | Human RA | — | — | No effect in vivo and ex vivo [21] | ↓ in vivo and in vitro [73, 76] | Improved [99] |
| IL-17a | AIA mouse model and human RA | ↑ in the joint [22, 23] | ↑ in vivo [22] | — | ↑ in vitro [13] | |
| Adenoviral vectors with IL-17 | IC-mediated arthritis mouse model | — | ↑ in vivo [38] | — | — | Deteriorated [38] |
| Anti-IL-17 antibody administration | CIA model | — | ↓ in vivo [44] | — | ↓ in vitro [13] | Improved [44] |
| IL-23 | AIA mouse model and human RA | ↑ in joint [22, 24] | ↑ in vivo [22] | — | — | — |
| IL-22 | AIA mouse model and human RA | ↑ in synovial tissue [25, 26] | ↑ in vivo [25] | — | — | — |
| Block IL-22 or IL-22−/− | AIA mouse model | — | ↓ in vivo [25] | — | — | Improved [25] |
| rmIL-22 administration | Normal mice | — | ↑ in vivo [25] | — | — | Deteriorated [25] |
| IL-1β | Human RA and AIA mouse model | ↑ in synovial fluid [19] | ↑ in vitro [25] | Delayed apoptosis in vitro [62] | ↑ in vitro [81–83] | — |
| IL-1R−/− or IL-1R antagonist | Collagen Ab and LPS-inducedarthritis model | — | ↓ in vivo [52] | — | ↓ in vitro [82, 83] | Improved [52] |
| IL-8 | Arthritis rabbit model and human RA | ↑ in synovial fluid [19, 27] | ↑ in vivo [39], ↑ in vitro [58] | No effect in vitro [27] | ↑ in vitro [13] | — |
| Blockade of IL-8 | Arthritis rabbit model | — | ↓ in vivo [39] | — | — | Improved [39] |
| IL-10 | Human RA | ↑ in synovial fluid [19] | — | — | ↑ in vitro [100] | — |
| IFN-γ | Human RA | ↑ in synovial fluid [19] | — | Delayed apoptosis in vitro [58] | ↑ in vitro [79] | — |
| IFN-γ−/− | AIA, CIA model | — | ↑ in vivo [43, 44] | — | — | Deteriorated [43, 44] |
| GM-CSF | Human RA | ↑ released by RAFLS in vitro [28], ↑ in serum and synovial fluid [18, 29, 30] | — | Survival ↑ [28], delayed apoptosis in vitro [27, 57, 58] | No effect in vitro [13] | — |
| Blockade of GM-CSF | CIA | — | ↓ neutrophils in the joint [48] | — | — | Improved [48] |
| GM-CSF−/− | K/BxN serum transfer arthritis | — | ↓ neutrophils in the joint [48] | — | — | Improved [48] |
| G-CSF | Human RA | ↑ in serum and synovial fluid [30, 31] | — | — | ↑ in vitro [101] | — |
| rhG-CSF | CIA | ↑ serum G-CSF [51] | ↑ in vivo [51] | — | — | Deteriorated [51] |
| G-CSF−/− | CIA | — | ↓ in vivo [51] | — | — | Improved [51] |
| mAb to G-CSF receptor | Collagen Ab-induced arthritis model | — | ↓ in vivo [47] | — | — | Improved [47] |
| IL-9 | Human RA | ↑ in serum and synovial fluid [32, 33] | — | Delayed apoptosis [32] | ↑ in vitro [85] | — |
| IL-15 | Human RA | ↑ in synovial fluid [34] | ↑ in vivo [45] | Delayed apoptosis in vitro [27] | ↑ in vitro [100] | |
| IL-18 | Human RA | ↑ in serum, synovial tissue and fluid [35] | ↑ in vivo [53] | No effect in vitro [59] | ↑ in vitro [100] | |
| IL-33 | mBSA-immunized mouse model | ↑ mRNA expression [11] | ↑ in vivo [11] | — | ↑ in vitro [86] | |
| rmIL-33 | rmIL-33 local injection | — | ↑ in vivo [11] | — | — | Deteriorated [11] |
| Blockade of IL-33 | mBSA-immunized mouse model | — | ↓ in vivo [11] | — | — | Improved [11] |
| IL-37 | Human RA | ↑ in serum and synovial fluid [36] | — | — | — | |
| IL-37 administration | CIA and streptococcal cell wall fragments induced arthritis | — | ↓ in vivo [54] | — | — | Improved [54, 102] |
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