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

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.

Study Overview

• Status: Completed
• Conditions: Systemic Inflammatory Response Syndrome (SIRS)

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 54

Contacts and Locations

Study Locations

• Czechia
  • Prague, Czechia, 12000
    • General University Hospital in Prague

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Study group consisted of patients admitted to General University Hospital in Prague with acute illness fulfilling the inclusion criteria. Healthy controls consisted of healthy volunteers free of acute or chronic illnesses that could confound study outcomes (any autoimmune, inflammatory, cardiovascular, metabolic, or other systemic disease requiring treatment).

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
SIRS patients; Patients admitted to hospital with acute illness fulfilling criteria for systemic inflammatory response syndrome (SIRS).
Healthy Controls; Healthy individuals without acute or chronic disease, matched to patients by age and sex where applicable.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospital stay	Total number of days from hospital admission to hospital discharge alive.	From hospital admission until hospital discharge (up to 90 days).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline circulating myostatin level	Association between baseline serum myostatin concentration and clinical and functional parameters.	Within 48 hours after hospital admission.
Baseline circulating irisin level	Association between baseline serum irisin concentration and clinical and functional parameters.	Within 48 hours after hospital admission.
Quadriceps muscle thickness	Association between ultrasound-derived measurement of quadriceps femoris muscle thickness and clinical and functional parameters	Baseline (within 48 hours after admission) and day 10 of hospitalization.
Handgrip strength	Muscle strength measured using a handheld dynamometer and its associations with clinical and functional parameters.	Baseline (within 48 hours after admission) and day 10 of hospitalization.
Composite adverse outcome (BAD)	Composite outcome defined as hospital length of stay above the 75th percentile, ICU length of stay above the 75th percentile, transfer to long-term care facility, or death.	During hospitalization (up to 90 days).

Collaborators and Investigators

• Sponsor: Charles University, Czech Republic
• Collaborators: General University Hospital, Prague

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2023
• Primary Completion (Actual): April 7, 2025
• Study Completion (Actual): November 11, 2025

Study Registration Dates

• First Submitted: March 12, 2026
• First Submitted That Met QC Criteria: March 12, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: critical illness; systemic inflammation; myokines; muscle ultrasound
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Inflammation; Shock; Pathological Conditions, Signs and Symptoms; Critical Illness; Systemic Inflammatory Response Syndrome
• Other Study ID Numbers: GIP-23-SL-06

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No