Calprotectin Is a Circulating Biomarker and Potential Therapeutic Target for Sarcopenia in Chronic Obstructive...

Sarcopenia, an important complication of chronic obstructive pulmonary disease (COPD), is significantly associated with increased mortality. Systemic inflammation is an important trigger of COPD-related skeletal muscle dysfunction. Calprotectin is a damage-associated molecular pattern involved in the inflammatory response, but its exact role and mode of action in COPD-related skeletal muscle dysfunction remain unclear. This study aimed to determine whether calprotectin is involved in COPD-related sarcopenia.

In this study, 235 patients with stable COPD were divided into the development (n = 117) and validation (n = 118) groups, and serum calprotectin concentrations were measured by enzyme-linked immunosorbent assays (ELISAs). Paquinimod, an oral calprotectin-specific inhibitor, was used to investigate the involvement of calprotectin in cigarette smoke (CS)-induced skeletal muscle dysfunction in vivo.

Handgrip strength and quadriceps muscle strength, essential indicators of muscle strength, were negatively correlated with serum calprotectin levels (r = -0.367, p < 0.001; r = -0.409, p < 0.001). The 5-time sit-to-stand test results, which reflect endurance and physical strength, were positively correlated with serum calprotectin levels (r = 0.290, p = 0.006). Ultrasound measurement of the rectus femoris muscle revealed negative correlations of serum calprotectin levels with both muscle thickness (r = -0.448, p < 0.001) and cross-sectional area (r = -0.495, p < 0.001). Furthermore, serum calprotectin levels were significantly greater in patients with sarcopenia than in those without sarcopenia (90.09 ± 25.72 ng/mL vs. 59.56 ± 23.22 ng/mL, p < 0.001). Importantly, serum calprotectin levels could effectively predict sarcopenia in COPD patients in the development set (AUC = 0.811) and validation set (AUC = 0.805). In C57BL/6 mice with CS-induced muscle dysfunction, paquinimod (10 mg/kg/day) reduced CS-induced muscle mass loss (skeletal muscle weight 1.15% ± 0.09% vs. 1.33% ± 0.09%; p = 0.005) and increased the muscle cross-sectional area (1375 ± 536.9 μm² vs. 2094 ± 470.2 μm²; p < 0.001). Paquinimod also reduced CS-induced muscle weakness, as indicated by increased grip strength (214.9 ± 31.38 g vs. 333.1 ± 34.93 g; p < 0.01). Paquinimod inhibited ubiquitin-proteasome system activity, reduced protein degradation marker levels, attenuated oxidative stress and increased antioxidant enzyme levels in CS-exposed mice.

Serum calprotectin levels can be used to accurately predict sarcopenia in patients with COPD, and the calprotectin inhibitor paquinimod is a potential treatment for CS-induced skeletal muscle dysfunction.