Myostatin and Irisin Levels in Predicting the Outcome of Patients With Systemic Inflammation: A Prospective Observational Study

Overview

Systemic inflammatory response syndrome (SIRS) is associated with severe metabolic stress that can lead to rapid breakdown of skeletal muscle and the development of stress-related malnutrition. These processes often result in muscle weakness, delayed recovery, prolonged hospital stay, and increased morbidity and mortality in affected patients. In recent years, increasing attention has been paid to signaling molecules produced by skeletal muscles, known as myokines. Myokines influence not only muscle regeneration and muscle breakdown but also have a wide range of effects on other organs and tissues in the body, including the brain and gastrointestinal tract. Previous studies suggest that lower levels of certain myokines, such as myostatin and irisin, may be associated with worse outcomes in critically ill patients. The primary aim of this prospective observational study is to evaluate the association between the levels of selected myokines and prolonged hospital stay in patients with systemic inflammation. If such an association is confirmed, myokines could potentially serve as prognostic biomarkers for the development of muscle dysfunction and prolonged hospitalization. Secondary objectives include evaluating correlations between myokine levels and other indicators of systemic inflammation and muscle dysfunction. In addition, the study assesses the potential use of bedside ultrasound measurement of the quadriceps muscle to detect muscle catabolism and to help predict clinical outcomes in hospitalized patients.

Muscle weakness develops in a substantial proportion of critically ill patients and is particularly common among those with systemic inflammatory conditions, especially sepsis. The pathogenesis of muscle weakness in critical illness is multifactorial and includes persistent catabolic metabolism, immobilization, and mechanical ventilation, as well as molecular alterations such as mitochondrial dysfunction, oxidative stress, impaired autophagy, and changes in ion channel regulation. These processes lead to accelerated muscle atrophy and functional impairment. Skeletal muscle also plays an active role in systemic metabolic and inflammatory processes through the secretion of myokines, a group of peptide or protein signaling molecules with autocrine, paracrine, and endocrine effects. Among the best characterized myokines are myostatin and irisin. Myostatin is known to inhibit muscle protein synthesis and promote muscle protein degradation, thereby suppressing muscle growth and differentiation. Irisin has been associated with regulation of thermogenesis, energy metabolism, and skeletal muscle adaptation. Previous studies have suggested that circulating levels of these myokines may be associated with metabolic dysfunction, muscle mass, and clinical outcomes in various patient populations. However, prospective clinical studies examining the role of myokines in patients with systemic inflammatory states remain limited. This single-center prospective observational pilot study aims to investigate the relationship between circulating levels of myostatin and irisin and clinical outcomes in patients with systemic inflammatory conditions. In addition to clinical outcomes, the study evaluates associations between myokine concentrations and laboratory markers of inflammation, anthropometric parameters, muscle strength, and ultrasound-derived measures of quadriceps muscle thickness. Bedside ultrasound measurement of quadriceps muscle thickness is also evaluated as a potential non-invasive method for monitoring muscle loss during acute illness. The study was registered retrospectively after completion of participant enrollment.