Table 5

Overview of anti-inflammatory cytokines relevant to macrophage (dys)function in rheumatoid arthritis

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]

Main regulator of connective tissue remodelling

Potent inducer of hyaluronan synthase 1

Induces synovial inflammation (reviewed in [80]) but also suppresses acute and chronic arthritis [81,82]

Induces inflammation and cartilage degradation in a rabbit model [140]

Possesses autocrine features

MMP can affect TGF-β via shedding of latent TGF-β attached to decorin (disease-enhancing loop).


IFN-β, interferon-beta; IL, interleukin; IL-1RA, interleukin-1 receptor antagonist; Mφ, macrophage(s); RA, rheumatoid arthritis; TGF-β, transforming growth factor-beta. Reproduced with permission from Kinne RW, Stuhlmuller B, Palombo-Kinne E, Burmester GR: The role of macrophages in rheumatoid arthritis. In Rheumatoid Arthritis. Edited by Firestein GS, Panayi GS, Wollheim FA. New York: Oxford University Press; 2006:55–75 [2].

Kinne et al. Arthritis Research & Therapy 2007 9:224   doi:10.1186/ar2333