The proinflammatory and chondral activities of leukemia inhibitory factor in goat joints are partially a function of interleukin-1.
We wished to determine if the effects of injected recombinant human leukemia inhibitory factor (LIF) are a function of endogenous goat interleukin-1 (IL-1) production and, conversely, if the effects of injected recombinant human IL-1 are a function of endogenous LIF production in goat radiocarpal joints (RCJ). In preliminary experiments, murine LIF binding protein (MuLBP) and recombinant HuIL-1RA were found to independently attenuate the cartilage proteoglycan resorbing activity of goat synovial membrane-conditioned medium (GSMCM), implying activity against goat LIF and goat IL-1, respectively. The present study shows that the proinflammatory and chondral actions of rHuLIF in goat RCJ are partially attenuated by rHuIL-1RA. This implies that a small but important component of the in vivo activity of rHuLIF is a result of IL-1 production in the synovial joint. With the exception of proteoglycan synthesis, the absence of significant effects by MuLBP on the actions of rHuIL-1alpha in goat RCJ suggests that the proinflammatory and chondral effects of IL-1alpha in vivo are probably not mediated by LIF.
Bell
M C
MC
Department of Rheumatology and the Research Centre, Royal Perth Hospital, Western Australia, Australia.
Carroll
G J
GJ
Chapman
H M
HM
Mills
J N
JN
Layton
M J
MJ
Saklatvala
J
J
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects; D017077:Culture Media, Conditioned; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D007375:Interleukin-1 / Q000502:physiology*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000494:pharmacology*; D051379:Mice; D011509:Proteoglycans / Q000096:biosynthesis; D018121:Receptors, Cytokine / Q000378:metabolism; D053606:Receptors, OSM-LIF; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical; D013583:Synovial Membrane / Q000187:drug effects*
D017077:Culture Media, Conditioned; D006131:Growth Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; D008222:Lymphokines; D011509:Proteoglycans; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D011994:Recombinant Proteins