Background/Purpose:

Sarcopenic obesity and the associated risk of cardiovascular disease (CVD) and mortality in rheumatoid arthritis (RA) may be related to dysregulated skeletal muscle remodeling (Huffman et al. Arthritis Research & Therapy (2017); 19:12). Skeletal muscle remodeling relies on coordinated signaling through cytokines and myokines. We hypothesized that exercise training-induced alterations in muscle cytokines and myokines would reprogram muscle remodeling differently in (RA) versus those with prediabetes (PD). In this study, we investigated relationships between skeletal muscle cytokines and myostatin in patients with RA and PD before and after a high-intensity interval-based training (HIIT) program.

Methods:

All RA patients in this study satisfied 1987 ACR criteria. Body composition was assessed with Bod Pod^¨.  Using vastus lateralis biopsies, muscle (m) cytokines, mIL-1β, mIL-6, mIL-8, mTNF-α, mIL-10, and myostatin were quantified in RA (n=12) and pre-DM (n=9) before and after a 10-week supervised HIIT program. Continuous variables were compared using Students t-tests and Wilcoxon signed rank tests, dependent on normality. Correlations between muscle cytokines and clinical variables were compared using Spearmans rho.

Results:

The RA group was younger (age 63.9 vs 71.4 y; p<0.05) and thinner (BMI 27.4 vs 29.4 kg/m²; p<0.05) with similar cytokine yet lower muscle myostatin concentrations (Table 1). For both groups after HIIT training, there were no significant responses in cytokines or myostatin concentrations. While overall body composition changes were small in RA, an increase in lean mass correlated with decreases in mIL-6, mIL-1 β, and mTNF-α. A decrease in body fat percentage was correlated with a decrease in mTNF-α.

Conclusion:

While muscle cytokines in RA were comparable to an older, heavier, prediabetic group, RA myostatin was lower. As a potent negative regulator of skeletal muscle growth and hypertrophy, lower muscle myostatin suggests that in RA, sarcopenic obesity may be related to impaired myostatin signaling. Although 10 weeks of HIIT did not significantly alter mean group cytokine or myostatin concentrations, reductions in RA muscle cytokines were associated with improved body composition (greater lean mass and less body fat percentage). Thus, HIIT may improve coordination of cytokines and myokines critical for skeletal muscle remodeling.

Table 1

Continuous variable data are presented as means (SD). IL interleukin, TNF tumor necrosis factor, HIIT high intensity interval training

*p < 0.05 for comparisons between RA and pre-diabetes mellitus groups