Interleukin-6 (IL-6) and Tumor necrosis factor-alpha (TNF-alpha) (IL-6 and TNF-alpha)

Interleukin-6 (IL-6) and Tumor necrosis factor-alpha (TNF-alpha) are pivotal pro-inflammatory cytokines that significantly influence muscle metabolism by shifting the balance toward catabolism. These molecules are primary mediators of muscle wasting (cachexia) in chronic diseases such as cancer, heart failure, and rheumatoid arthritis (PubMed: 23648338). TNF-alpha, also known as cachectin, triggers muscle protein degradation via the NF-kappaB pathway, while IL-6 primarily signals through the JAK/STAT3 pathway to induce atrophy-related genes (atrogenes) like MuRF-1 and Atrogin-1 (PubMed: 30116498). Together, they suppress muscle protein synthesis by inhibiting the anabolic IGF-1/mTOR signaling axis. Pharmacological inhibition of these cytokines using monoclonal antibodies like tocilizumab (anti-IL-6R) or infliximab (anti-TNF) is a common strategy in inflammatory disorders and is being investigated for its potential to mitigate muscle loss (StatPearls: NBK493171).

Other names

IL6TNFTNFACachectinB-cell stimulatory factor 2BSF-2Tumor necrosis factor ligand superfamily member 2Interleukin 6Tumor necrosis factor alpha

Neutralization of circulating cytokines or blockade of their specific receptors to inhibit downstream catabolic signaling pathways in skeletal muscle (PubMed: 23648338).