Is there a rationale for combined TNF and IL-1 blocking in arthritis?
TNF and IL-1 are master cytokines in chronic destructive arthritis. Therapeutic approaches have so far focused mainly on TNF which is a major inflammatory mediator in RA and a potent inducer of IL-1. Anti-TNF treatment shows great efficacy in RA patients. However, it is not effective in all patients, nor does it fully control the arthritic process in affected joints of good responders. Although TNF is an early mediator and often crucial in onset of experimental arthritis, studies in rodent models revealed that TNF independent IL-1 production does occur in many arthritic situations. These include direct, innate macrophage activation by phlogistic stimuli, but also immune driven conditions of immune complex and T cell mediated arthritis. If elements of the models apply to the arthritic process in RA patients, it is necessary to block IL-1 in addition to TNF.
van den Berg
W B
WB
Rheumatology Research and Advanced Therapeutics, University Medical Center Nijmegen, The Netherlands. w.vandenberg@reuma.azn.nl
D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy* / Q000276:immunology*; D004359:Drug Therapy, Combination; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D023421:Models, Animal; D009363:Neoplasm Proteins / Q000276:immunology / Q000627:therapeutic use; D051381:Rats; D047889:Receptors, Tumor Necrosis Factor, Type II; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
D018501:Antirheumatic Agents; D007375:Interleukin-1; D009363:Neoplasm Proteins; D047889:Receptors, Tumor Necrosis Factor, Type II; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha