Muscle wasting in an acute Poly(I:C) and cigarette smoke-induced pulmonary inflammation mouse model

Cachexia occurs frequently in patients with COPD and is a strong independent risk factor for mortality. Our aim was to study the effect of Prednisolone and a ghrelin agonist on muscle atrophy in an acute mouse model of pulmonary inflammation. Methods: Mice were exposed to CS during four days. Saline or PIC was administered intranasally. Mice receiving combined CS+PIC were treated orally once daily with vehicle, Prednisolone (10 mg/kg) or BID with Capromorelin (8 and 20 mg/kg). Muscles weight on the hind limb (QS, GN, EDL and soleus) were weighed at termination. Results: There were no significant effect of CS exposure (5%, p=0.13) or PIC treatment (-3%, p=0.42) alone on the muscle loss. A significant additive effect (11%, p = 0.01) was observed in the CS+PIC group. Prednisolone significantly reduced IL-1B, IL-6, IL-10 and IL-12 in BAL and plasma. Prednisolone itself caused a 10% (p=0.01) muscle loss and the effect in CS+PIC group was 22% (p Conclusions: Five days CS exposure in combination with PIC treatment causes significant loss in bodyweight and muscles. Prednisolon reduced the acute inflammation but worsened the muscle atrophy. Our results show that a ghrelin agonist could reduce the muscle loss in a mouse model of acute pulmonary inflammation. The described animal model may be useful for investigating effects on muscle atrophy for agents aimed as treatments for COPD.