Eccentric exercise results in a prolonged increase in interleukin-6 and tumor necrosis factor-α levels in rat skeletal muscle
Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) are well-known cytokines with pro-inflammatory capabilities, and have been shown to be involved in adaptation to exercise as multifaceted myokines. However, the precise role of IL-6 and TNF-α during exercise-induced skeletal muscle injury and subsequent repair processes is not fully understood. In this study, IL-6 and TNF-α were examined in soleus muscles at the gene and protein levels using in situ hybridization and immunohistochemical staining, respectively, and serum levels of IL-6 and TNF-α were determined before and after a 90-min downhill running session in rats. There were no changes in serum levels of IL-6 and TNF-α after exercise, but IL-6 and TNF-α mRNA increased and maintained high expression in muscles for 1–2 weeks after exercise. IL-6 and TNF-a mRNAs were identified in both the cytoplasm and the nuclei of myocytes, as well as in invading inflammatory cells. IL-6 and TNF-α protein mainly distributed in cytoplasm unevenly and had a prolonged expression until 2 weeks after eccentric exercise. Our results demonstrate that there is increased IL-6 and TNF-α expression in skeletal muscle that is induced by eccentric exercise and that the high expression of IL-6 and TNF-α in the long-term phase after eccentric exercise may be more involved in the subsequent recovery of damaged muscle.
KeywordsDownhill running Damaged muscle Interleukin-6 Tumor necrosis factor-alpha
Tumor necrosis factor-alpha
This study was supported by: (1) Natural Science Foundation of Shanghai (CN) (No. 10ZR1429000). (2) Key Laboratory of Human Sports Capability Development and Protection (Shanghai University of Sport, No. 11DZ2261100).
- Armstrong RB, Ogilvie RW, Schwane JA (1983) Eccentric exercise-induced injury to rat skeletal muscle. J Appl Physiol Respir Environ Exerc Physiol 54:80–93Google Scholar
- Cantini M, Massimino ML, Rapizzi E, Rossini K, Catani C, Dalla Libera L, Carraro U (1995) Human satellite cell proliferation in vitro is regulated by autocrine secretion of IL-6 stimulated by a soluble factor(s) released by activated monocytes. Biochem Biophys Res Commun 216:49–53CrossRefGoogle Scholar
- Davis JM, Murphy EA, Carmichael MD, Zielinski MR, Groschwitz CM, Brown AS, Gangemi JD, Ghaffar A, Mayer EP (2007) Curcumin effects on inflammation and performance recovery following eccentric exercise-induced muscle damage. Am J Physiol Regul Integr Comp Physiol 292:R2168–R2173CrossRefGoogle Scholar
- Kuru S, Inukai A, Kato T, Liang Y, Kimura S, Sobue G (2003) Expression of tumor necrosis factor-alpha in regenerating muscle fibers in inflammatory and non-inflammatory myopathies. Acta Neuropathol 105:217–224Google Scholar
- Plomgaard P, Penkowa M, Pedersen BK (2005) Fiber type specific expression of TNF-αlpha, IL-6 and IL-18 in human skeletal muscles. Exerc Immunol Rev 11:53–63Google Scholar
- Wehling-Henricks M, Li Z, Lindsey C, Wang Y, Welc SS, Ramos JN, Khanlou N, Kuro-O M, Tidball JG (2016) Klotho gene silencing promotes pathology in the mdx mouse model of Duchenne muscular dystrophy. Hum Mol Genet 25:2465–2482Google Scholar
- Yu X, Zuo Q, Chao W, Jiang R (2013) The changes of muscle FGF-6 expression at different time points after exercise-induced muscle damage. West Indian Med J 62:793–798Google Scholar