Muscle Inflammation and Change in Neutrophil Concentration after Repeated Eccentric Exercise

diverse mechanisms such as mechanical injury, muscular dystrophies, infectious diseases, and biochemical toxicities. Several types of skeletal muscle injury fall into the broad category of sport and exercise induced muscle injury. When exercise involves eccentric muscular contractions, it is associated with overloading of the contractile elements and connective tissues—that is, the force requirement of the muscle exceeds the habitual requirements—and can result in injury to skeletal muscle. It has traditionally been felt that the events following the initial injury, including inflammation, are necessary for optimal repair. The inflammatory response to eccentric exercise as well as stretch injury consist of neutrophilia, neutrophil activation, and the accumulation of neutrophils within the injured muscle as early as one to two hours. In this early inflammatory stage, cellular debris is removed by the infiltrating neutrophils and is followed by a regenerative response during which satellite cells proliferate to replace the previously damaged and phagocytosed muscle. In addition to phagocytosis, neutrophil invasion and activation can lead to the release of oxygen free radicals and proteases which potentially cause injury. Neutrophils contain more than 40 hydrolytic enzymes and toxic molecules in their granules and can generate various oxidants such as superoxide anion, hydrogen peroxide, and hypochlorous acid. The NADPH oxidase complex located on activated neutrophils and macrophages can initiate a “respiratory burst” which leads to production of superoxide anion, which can quickly be converted into hydrogen peroxide. In addition, myeloperoxidase, an enzyme present in neutrophils and macrophages, can generate hypochlorous acid, a highly reactive oxidising agent. Although the exact time course of the appearance of inflammatory cells and secondary muscle damage is debated, recent studies of single stretch injury have highlighted that peak damage occurs at the same time as maximum neutrophil invasion of the injured tissue, 7 prompting the idea that neutrophils may somehow participate in causing injury (fig 1). We will examine the relation between muscle injury and change in neutrophil concentration after both eccentric exercise and acute stretch injury. We will present evidence to suggest that invading leucocytes—that is, neutrophils and macrophages—exacerbate the initial mechanical damage. Although the clinical implications are not clear at this time, it is conceivable that limiting certain aspects of inflammation will present new treatment strategies for sport related muscle trauma. Perspectives for rational approaches to handle the development of muscle injury during neutrophil inflammation are considered.