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.

Title

The journal of physiology

Publisher

John Wiley & Sons, Inc.

Publisher Country

United States of America

Indexing

Thomson Reuters

Impact Factor

4.5

Publication Type

Both (Printed and Online)

Volume

599

Year

2021

Pages

2869-2886