JAK/STAT inhibition augments soleus muscle function in a rat model of critical illness myopathy via regulation of complement C3/3R
Publication Type
Original research

Critical illness myopathy (CIM) is frequently observed in response to modern critical care with negative consequences for patient quality of life, morbidity, mortality, and health care costs. JAK/STAT activation is observed in limb muscles following controlled mechanical ventilation (CMV). Chronic JAK/STAT activation promotes loss of muscle mass and function. Thus, we hypothesised that JAK1/2 inhibition would improve muscle outcomes for critical illness myopathy (CIM). Following 12 days intensive care unit (ICU) conditions, pSTAT‐3 levels increased in Tibialis anterior muscle of CIM patients (p = 0.0489). The potential of JAK1/2 inhibition was assessed in an experimental model of CIM, where soleus muscle size and force are impaired. JAK1/2 inhibition restores soleus force (p < 0.0001). CIM activated muscle complement cascade, which was ameliorated by JAK1/2 inhibition (p < 0.05, respectively). Soleus macrophage number corresponded with complement activity, leading to reduced muscle degeneration and augmented muscle function (p < 0.05). Thus, JAK/STAT inhibition improves soleus function by modulating the complement cascade and muscle monocyte infiltration. Collectively, we demonstrate that JAK/STAT inhibition augments muscle function in CIM.

The journal of physiology
John Wiley & Sons, Inc.
Publisher Country
United States of America
Thomson Reuters
Impact Factor
Publication Type
Both (Printed and Online)