RESUMO
IL-6 is secreted from muscles to the circulation during high-intensity and long-duration exercise, where muscle-derived IL-6 works as an energy sensor to increase release of energy substrates from liver and adipose tissues. We investigated the mechanism involved in the exercise-mediated surge in IL-6 during exercise. Using interval-based cycling in healthy young men, swimming exercise in mice, and electrical stimulation of primary human muscle cells, we explored the role of lactate production in muscular IL-6 release during exercise. First, we observed a tight correlation between lactate production and IL-6 release during both strenuous bicycling and electrically stimulated muscle cell cultures. In mice, intramuscular injection of lactate mimicked the exercise-dependent release of IL-6, and pH buffering of lactate production during exercise attenuated IL-6 secretion. Next, we used in vivo bioimaging to demonstrate that intrinsic intramuscular proteases were activated in mice during swimming, and that blockade of protease activity blunted swimming-induced IL-6 release in mice. Last, intramuscular injection of the protease hyaluronidase resulted in dramatic increases in serum IL-6 in mice, and immunohistochemical analyses showed that intramuscular lactate and hyaluronidase injections led to release of IL-6-containing intramyocellular vesicles. We identified a pool of IL-6 located within vesicles of skeletal muscle fibers, which could be readily secreted upon protease activity. This protease-dependent release of IL-6 was initiated by lactate production, linking training intensity and lactate production to IL-6 release during strenuous exercise.
Assuntos
Interleucina-6/metabolismo , Ácido Láctico/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Adulto , Animais , Quimiocina CXCL1/metabolismo , Citocinas/metabolismo , Estimulação Elétrica , Exercício Físico , Humanos , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Ácido Láctico/farmacologia , Masculino , Metaloproteinase 2 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Camundongos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Condicionamento Físico Animal , Fator de Necrose Tumoral alfa/metabolismo , Adulto JovemRESUMO
Kinesiophobia is an irrational and debilitating fear of physical movement frequently occurring following anterior cruciate ligament (ACL) reconstruction. It is a major limiting factor in return to sport after ACL reconstruction and is associated with worse knee function and increased risk of a secondary ACL rupture. Kinesiophobia can be identified using the Tampa Scale of Kinesiophobia. Addressing kinesiophobia early in rehabilitation is crucial, as it can lead to non-adherence to rehabilitation. While cognitive therapy has shown promise in treating kinesiophobia, further research is needed in this area.