Cytokines and endotoxin induce cytokine receptors in skeletal muscle

Proinflammatory cytokines are important factors in the regulation of divers e aspects of skeletal muscle function; however, the muscle cytokine recepto rs mediating these functions are uncharacterized. Binding kinetics (dissoci ation constant = 39 +/- 4.7 x 10(-9) M, maximal binding = 3.5 +/- 0.23 x 10 (-12) mol/mg membrane protein) of muscle tumor necrosis factor (TNF) recept ors were obtained. Skeletal muscle was found to express mRNAs encoding inte rleukin-1 type I and II receptors, interleukin-6 receptor (IL-6R), and inte rferon-gamma receptor by RT-PCR, but these receptors were below limits of d etection of ligand-binding assay (greater than or equal to 1 fmol binding s ites/mg protein). Twenty-four hours after intraperitoneal administration of endotoxin to rats, TNF receptor type II (TNFRII) and IL-6R mRNA were incre ased in skeletal muscle (P< 0.05). In cultured L6 cells, the expression of mRNA encoding TNFRII and IL-6R receptors was induced by TNF-alpha, and all six cytokine receptor mRNA were induced by a mixture of TNF-alpha, IFN-gamm a, and endotoxin (P< 0.05). This suggests that the low level of cytokine re ceptor expression is complemented by a capacity for receptor induction, pro viding a clear mechanism for amplification of cytokine responses at the mus cle level.