IL-6-induced skeletal muscle atrophy

TLDR

Chronic low‑level IL‑6 elevation occurs in disease, aging, and after prolonged exercise, and has been linked to metabolic regulation, satellite cell proliferation, or muscle wasting. The study aimed to assess the direct impact of IL‑6 on skeletal muscle in the absence of systemic cytokine alterations. Using a rodent local infusion model that delivered modest IL‑6 levels into a single muscle, the authors measured cytokine and growth‑factor signaling markers and indicators of muscle atrophy. IL‑6 infusion induced muscle atrophy with a 17 % loss of myofibrillar protein, reduced phosphorylation of S6K and STAT5, increased STAT3 phosphorylation, and a shift toward catabolic signaling that likely contributes to IL‑6–induced atrophy.

Abstract

Chronic, low-level elevation of circulating interleukin (IL)-6 is observed in disease states as well as in many outwardly healthy elderly individuals. Increased plasma IL-6 is also observed after intense, prolonged exercise. In the context of skeletal muscle, IL-6 has variously been reported to regulate carbohydrate and lipid metabolism, increase satellite cell proliferation, or cause muscle wasting. In the present study, we used a rodent local infusion model to deliver modest levels of IL-6, comparable to that present after exercise or with chronic low-level inflammation in the elderly, directly into a single target muscle in vivo. The aim of this study was to examine the direct effects of IL-6 on skeletal muscle in the absence of systemic changes in this cytokine. Data included cellular and molecular markers of cytokine and growth factor signaling (phosphorylation and mRNA content) as well as measurements to detect muscle atrophy. IL-6 infusion resulted in muscle atrophy characterized by a preferential loss of myofibrillar protein (−17%). IL-6 induced a decrease in the phosphorylation of ribosomal S6 kinase (−60%) and STAT5 (−33%), whereas that of STAT3 was increased approximately twofold. The changes seen in the IL-6-infused muscles suggest alterations in the balance of growth factor-related signaling in favor of a more catabolic profile. This suggests that downregulation of growth factor-mediated intracellular signaling may be a mechanism contributing to the development of muscle atrophy induced by elevated IL-6.