Emerging cytokine targets in rheumatoid arthritis.
OBJECTIVE
The utility of cytokines as therapeutic targets in rheumatoid arthritis has been unequivocally demonstrated by the success of tumour necrosis factor blockade in clinical practice. Partial and non-responses to tumour necrosis factor blocking agents, however, together with the increasing clinical drive to remission induction, requires that further therapeutic targets be identified.


RESULTS
Numerous cytokine activities with pathogenetic potential have now been demonstrated in rheumatoid arthritis synovial membrane, including members of the IL-1 superfamily and the IL-12 superfamily. Continued efforts are ongoing to target IL-6 and IL-15 in clinical trials with promising data emerging. There is particular interest in the biology of IL-17 and of the recently described IL-32 as critical effector mediators.


CONCLUSIONS
Novel cytokine activities are emerging on an ongoing basis. There remain difficulties in ascribing the optimal regulatory hierarchy for given moieties on the basis of existing preclinical model systems. This in turn poses novel challenges in determining which cytokines represent the best therapeutic targets.
Asquith
Darren L
DL
Glasgow Biomedical Research Centre, Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, UK.
McInnes
Iain B
IB
D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000628:therapy*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D019409:Interleukin-15 / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D018448:Models, Immunological; D015398:Signal Transduction
D016207:Cytokines; C496971:IL32 protein, human; C508600:IL6 protein, human; D007375:Interleukin-1; D019409:Interleukin-15; D053759:Interleukin-23; D015850:Interleukin-6; D007378:Interleukins; D018664:Interleukin-12