Modulation of inflammation-induced changes in insulin-like growth factor (IGF)-I and IGF binding protein-1 by anti-TNF antibody.
The aim of the present study was to characterize changes in the insulin-like growth factor (IGF) system produced by the nonbacterial nonendotoxic inflammatory agent zymosan and to determine whether these changes were mediated by enhanced production of tumor necrosis factor (TNF). Rats were injected intraperitoneally with either zymosan or saline and studied 18 h later. Animals were pretreated with either nonimmune IgG or neutralizing anti-TNF antibody 2 h before zymosan injection. Zymosan increased the plasma concentration of TNF alpha, and this was associated with a decrease (approximately 40%) in the IGF-I concentration in plasma, liver, heart, and brain. The IGF-I content was not altered in skeletal muscle and kidney. Zymosan also increased the concentration of IGF binding protein (BP)-1 in plasma (120%), liver (90%), and muscle (470%). Circulating TNF alpha was not detectable in rats injected with anti-TNF antibody before zymosan. The neutralizing antibody prevented the zymosan-induced reduction in IGF-I in plasma and blunted the decreased observed in liver, but did not alter the decrease in heart or brain. Anti-TNF antibody also attenuated (40-60%) the increased IGFBP-1 in plasma, liver, and muscle observed in zymosan-treated rats. We conclude that zymosan-induced inflammation not only decreases IGF-I in plasma and selected tissues, but also increases IGFBP-1 in plasma, liver, and muscle, and that these alterations are due in large part to the enhanced production of TNF alpha.
Fan
J
J
Department of Surgery, State University of New York at Stony Brook 11794-8191, USA.
Li
Y H
YH
Bagby
G J
GJ
Lang
C H
CH
D000818:Animals; D000911:Antibodies, Monoclonal; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D007074:Immunoglobulin G / Q000008:administration & dosage; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000187:drug effects / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D015054:Zymosan / Q000633:toxicity*
D000911:Antibodies, Monoclonal; D001786:Blood Glucose; D007074:Immunoglobulin G; D018970:Insulin-Like Growth Factor Binding Protein 1; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I; D015054:Zymosan