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

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.

Inclusion criteria

• Age ≥18 years
• Hospital admission with acute illness
• Presence of systemic inflammatory response syndrome (SIRS) defined by at least two of the following:

body temperature >38°C or <36°C heart rate >90 bpm respiratory rate >20/min or PaCO₂ <4.3 kPa leukocytosis >12 × 10⁹/L or leukopenia <4 × 10⁹/L

• Expected hospital stay ≥5 days
• Ability to provide informed consent

Exclusion criteria

• Transfer from another hospital with prior hospitalization >48 hours
• Terminal illness (malignant or non-malignant)
• Long-term immobility prior to hospital admission
• Conditions preventing participation in study procedures