Introduction: Defects in mitochondrial function and increased circulating interleukin-6 (IL-6) caused by uremia of chronic kidney disease (CKD) are significant contributors to skeletal muscle atrophy and weakness, and to increased mortality. This study evaluated the effect of abrogation of IL-6 on markers of muscle and mitochondrial dysfunction.
Methods: Adenine supplementation was used to induce uremia in wild-type (WT) and IL-6-knockout (KO) mice, which were compared to control diet WT and IL-6-KO mice, respectively. Body weight, individual muscle weights, quantity and diameter of extensor digitorum longus (EDL) fibers by type (1, 2A, 2B and 2X), optical density of mitochondrial complexes (I-V) in the gastrocnemius and gastrocnemius expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α, a key positive regulator of mitochondrial biogenesis and function) were compared using descriptive statistics.
Results: Compared to controls, uremic WT mice had reduced body and individual muscle weights, significant changes in size of EDL fibers across all fiber types, decreased optical density of complexes I-V in gastrocnemius mitochondria, and reduced gastrocnemius expression of PGC1α. Uremic IL-6-KO mice did show reduced body and individual muscle weights compared to control IL-6-KO mice, but showed no significant changes in size of EDL fibers by type, no change in optical density of complexes I-V in gastrocnemius mitochondria, and equivalent gastrocnemius expression of PGC1α compared to controls.
Discussion: These data indicate that IL-6 directly disrupts mitochondrial function demonstrate specific mitochondrial targets of its action. IL-6 may be an important therapeutic target to improve quality of life and mortality in CKD patients.
Recommended CitationPenzel, Taylor and Martinez Cantarin, Maria P., "Role of IL-6 in Uremia-Induced Muscle Dysfunction" (2021). Phase 1. Paper 8.