Table 4

Overview of pro-inflammatory interleukins relevant to macrophage (dys)function in rheumatoid arthritis

Family

Cytokine

Pro-inflammatory

Dual

Autocrine

Main pathogenetic features


IL-1

IL-1

X

-

X

Predominantly produced by Mφ

Critical mediator of tissue damage

Possesses autocrine features [43,51-53]

IL-18

X

-

X

Predominantly produced by Mφ

Critical pleiotropic mediator of disease

Possesses autocrine features [59-61]

IL-33

X

X

-

Produced by endothelial cells

Important Th2-inducing component in allergy/autoimmunity

Signals via IL-1 receptor-related protein (ST2)

Nuclear factor with transcriptional repressor properties (≈ nuclear factor from high endothelial venules) [111-113]

IL-18 inducible

IL-32

X

-

-

Pro-inflammatory effects on both myeloid and non-myeloid cells [114,115]

IL-2

IL-7

X

-

-

Elevated in RA, although a relative paucity is also possible [116,117]

Induces osteoclastic bone loss in mice [118]

IL-15

X

-

X

Produced by Mφ

Important autocrine mediator of disease processes [21,56-58]

IL-21

X

-

-

Only IL-21R is expressed by synovial Mφ and fibroblasts [119]

IL-6

IL-6

X

X

-

Predominantly produced by fibroblasts under the influence of Mφ

Most strikingly elevated cytokine in acute RA, with phase-dependent differential effects [17,75,76] (reviewed in [2,77])

IL-31

X

-

-

Induces experimental dermatitis [120]

LIF

X

-

-

Stimulates proteoglycan resorption in cartilage [121]

Oncostatin M

X

-

-

Recruits leukocytes to inflammatory sites and stimulates production of metalloprotease (MMP) and tissue inhibitor of MMP [121]

IFN type I/IL-10

IL-19

X

-

X

Involved in both Th1 and Th2 inflammatory disorders [122,123]

Possesses autocrine features [124,125]

IL-20

X

-

X

Overexpressed in psoriasis

Possesses autocrine features [122]

IL-22

X

-

-

Relevant to innate immunity and acute-phase response [126]

IL-24

X

-

-

Possible antagonism with regulatory IL-10 [127]

IL-26

X

-

-

Polymorphism possibly contributes to RA sex-bias susceptibility [128]

IL-28, IL-29

X

-

X

Involved in microbial recognition by upregulation of Toll-like receptors

Possesses autocrine features [30,129,130]

IL-12

IL-12

X

-

-

Predominantly produced by synovial Mφ and dendritic cells

Promotes Th1 responses (reviewed in [62])

IL-23

X

-

-

Predominantly produced by synovial Mφ and dendritic cells

Shares p40 subunit with IL-12 and possibly antagonizes IL-12 [63] (reviewed in [62])

IL-27

X

X

X

Produced by Mφ and its neutralization has anti-arthritic effects

Possesses autocrine features [66]

Pro-inflammatory role [67]

IL-17

IL-17

X

-

-

Th0-Th1 lymphokine with pleiotropic, amplifying effects on Mφ arthritis (reviewed in [24,25])


IFN, interferon; LIF, leukemia inhibitory factor; Mφ, macrophages; RA, rheumatoid arthritis. 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