IL-1β, in contrast to TNFα, is pivotal in blood-induced cartilage damage and is a potential target for therapy.
Joint bleeding after (sports) trauma, after major joint surgery, or as seen in hemophilia in general leads to arthropathy. Joint degeneration is considered to result from the direct effects of blood components on cartilage and indirectly from synovial inflammation. Blood-provided proinflammatory cytokines trigger chondrocytes and induce the production of cartilage-degrading proteases. In the presence of erythrocyte-derived iron, cytokines stimulate radical formation in the vicinity of chondrocytes inducing apoptosis. To unravel the role of interleukin (IL) 1β and tumor necrosis factor (TNF) α in the pathogenesis of this blood-induced cartilage damage, the effect of antagonizing these cytokines was examined in human in vitro cultures. Addition of recombinant human IL-1β monoclonal antibody or IL-1 receptor antagonist resulted in a dose- and time-dependent protection of cartilage from blood-induced damage. In higher concentrations, almost complete normalization of cartilage matrix proteoglycan turnover was achieved. This was accompanied by a reduction in IL-1β and IL-6 production in whole blood cultures, whereas TNFα production remained unaffected. Interestingly, addition of a TNFα monoclonal antibody, although demonstrated to inhibit the direct (transient) effects of TNFα on cartilage, exhibited no effect on blood-induced (prolonged) cartilage damage. It is demonstrated that IL-1β is crucial in the development of blood-induced joint damage, whereas TNFα is not. This hierarchical position of IL-1β in blood-induced joint damage warrants studies on targeting IL-1β to potentially prevent joint degeneration after a joint bleed.
Van Creveldkliniek and Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
Lize F D
http://orcid.org/0000-0003-3242-5524
LF
van Vulpen
Van Creveldkliniek and.
Roger E G
RE
Schutgens
Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
Katja
K
Coeleveld
Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
Els C
EC
Alsema
Van Creveldkliniek and.
Goris
G
Roosendaal
Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
Simon C
SC
Mastbergen
Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
Floris P J G
FP
Lafeber
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001769:Blood; D002356:Cartilage / Q000276:immunology / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D002357:Cartilage Diseases / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; C508585:IL1B protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha