title: Insulin-like growth factor-1 activity is inhibited by interleukin-1 alpha, tumor necrosis factor-alpha, and interleukin-6.
abstract: With evidence that several proteins inhibit insulin-like growth factor (IGF) activity, we evaluated whether cytokines, which are elevated in many catabolic states, also affect IGF-1-mediated proteoglycan synthesis. Cartilage from hypophysectomized rats was exposed to the cytokines interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF-alpha) or interleukin-6 (IL-6) in the presence or absence of IGF-1. IL-1 alpha inhibited IGF-1-stimulated proteoglycan (PG) synthesis > 95% at 20 ng/ml (p < 0.01). TNF-alpha and IL-6 caused a maximum inhibition of 56 and 54%, respectively, both at 200 ng/ml. Only in the absence of IGF-1 did IL-1 alpha inhibit PG synthesis below unstimulated levels, suggesting that although IL-1 alpha can directly inhibit PG synthesis, IL-1 alpha, TNF-alpha, TNF-alpha, and IL-6 each promotes cartilage loss also by inhibiting IGF-1-mediated anabolism.
authors.affiliation: Department of Surgery, Cornell University Medical College, New York, NY 10021.
authors.forename: D D
authors.initials: DD
authors.lastname: Lazarus
authors.forename: L L
authors.initials: LL
authors.lastname: Moldawer
authors.forename: S F
authors.initials: SF
authors.lastname: Lowry
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051379:Mice; D009924:Organ Culture Techniques; D011509:Proteoglycans / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D011509:Proteoglycans; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I