The study investigates the role of nuclear factor kappa B (NF-κB) in cytokine-induced muscle degeneration, particularly focusing on the transcription factor MyoD, which is essential for skeletal muscle differentiation (SMD). TNF, a cytokine that activates NF-κB, was found to inhibit SMD by suppressing MyoD mRNA at the post-transcriptional level in differentiating C2C12 myocytes. In contrast, in differentiated myotubes, TNF plus interferon-γ (IFN-γ) signaling was required for NF-κB-dependent down-regulation of MyoD and dysfunction of skeletal myofibers. MyoD mRNA was also down-regulated by TNF and IFN-γ in mouse muscle in vivo. These findings suggest that NF-κB plays a crucial role in the skeletal muscle decay observed in cachexia, a condition characterized by extreme weight loss and whole-body wasting, often seen in patients with chronic diseases like cancer. The study proposes that direct inhibition of NF-κB may be beneficial in reducing muscle wasting associated with cachexia.The study investigates the role of nuclear factor kappa B (NF-κB) in cytokine-induced muscle degeneration, particularly focusing on the transcription factor MyoD, which is essential for skeletal muscle differentiation (SMD). TNF, a cytokine that activates NF-κB, was found to inhibit SMD by suppressing MyoD mRNA at the post-transcriptional level in differentiating C2C12 myocytes. In contrast, in differentiated myotubes, TNF plus interferon-γ (IFN-γ) signaling was required for NF-κB-dependent down-regulation of MyoD and dysfunction of skeletal myofibers. MyoD mRNA was also down-regulated by TNF and IFN-γ in mouse muscle in vivo. These findings suggest that NF-κB plays a crucial role in the skeletal muscle decay observed in cachexia, a condition characterized by extreme weight loss and whole-body wasting, often seen in patients with chronic diseases like cancer. The study proposes that direct inhibition of NF-κB may be beneficial in reducing muscle wasting associated with cachexia.