Table 5 Overview of anti-inflammatory cytokines relevant to macrophage (dys)function in rheumatoid arthritis
From: Cells of the synovium in rheumatoid arthritis. Macrophages
| Â | Anti-inflammatory | Dual | Autocrine | Main pathogenetic features |
|---|---|---|---|---|
IL-1RA | X | - | X | Produced by differentiated Mφ and upregulated by pro-inflammatory mediators, including IL-1 itself or granulocyte macrophage colony-stimulating factor Autocrine contribution to the termination of inflammatory reactions [54,55] (reviewed in [53,56]) |
IL-4 | X | - | - | Strong regulator of Mφ functions but virtually absent in synovial tissue [73,131-133] |
IL-10 | X | - | X | Produced by synovial Mφ Strong regulator of Mφ functions but relatively deficient in RA Possesses autocrine features [73,74] |
IL-11 | X | X | - | Regulator of Mφ functions in a paracrine regulatory loop with synovial fibroblasts [36,134] |
IL-13 | X | X | - | Selective regulator of Mφ functions Improves experimental arthritis (reviewed in [2,91]) |
IL-16 | X | X | - | Known as an anti-inflammatory molecule [135,136], IL-16 also has pro-inflammatory properties (that is, correlates with metalloprotease-3 levels, progression of joint destruction, and levels of other pro-inflammatory cytokines) [137,138]. |
IFN-β | X | - | - | Clear anti-inflammatory and anti-destructive effects in experimental arthritides Therapy attempts in human RA thus far have been unsuccessful [149]. |
TGF-β | X | X | X | Produced by Mφ [78-80] |
| Â | Â | Â | Â | Main regulator of connective tissue remodelling |
| Â | Â | Â | Â | Potent inducer of hyaluronan synthase 1 |
| Â | Â | Â | Â | Induces synovial inflammation (reviewed in [80]) but also suppresses acute and chronic arthritis [81,82] |
| Â | Â | Â | Â | Induces inflammation and cartilage degradation in a rabbit model [140] |
| Â | Â | Â | Â | Possesses autocrine features |
|  |  |  |  | MMP can affect TGF-β via shedding of latent TGF-β attached to decorin (disease-enhancing loop). |