Mechanical loading can counteract inflammatory pathways induced by IL-1 beta by inhibiting (NO)-N-. and PGE(2), catabolic mediators known to be involved in cartilage degradation. The current study investigates the potential of dynamic compression, in combination with the anti-inflammatory cytokine, IL-4, to further abrogate the IL-1 beta induced effects. The data presented demonstrate that IL-4 alone can inhibit nitrite release in the presence and absence of IL-1 beta and partially reverse the IL-1 beta induced PGE(2) release. When provided in cornbination, IL-4 and dynamic compression Could further abrogate the IL-1 beta induced nitrite and PGE(2) release. IL-1 beta inhibited [H-3]thymidine incorporation and this effect could be reversed by IL-4 or dynamic strain alone or both in combination. By contrast, (SO4)-S-35 incorporation was not influenced by IL-4 and/or dynamic strain in IL-1 beta stimulated constructs. IL-4 and mechanical loading may therefore provide a potential protective mechanism for cartilage destruction as observed in OA. (c) 2005 Elsevier Inc. All rights reserved.