TNF-alpha in an Overuse Muscle Model-Relationship to Muscle Fiber Necrosis/Regeneration, the NK-1 Receptor and an Occurrence of Bilateral Involvement

TNF-alphais known to be involved in muscle damage and inflammation (myositis). Therelationships between the TNF-alpha system and muscle fibernecrosis/regeneration and the tachykinin system in this situation are unclear.We have an experimental rabbit model related to unilateral muscle overuse whichleads to marked muscle derangement and myositis bilaterally. Using this model,staining for TNF-alpha, in parallel with staining for the substance P-preferredreceptor (NK-1R) and desmin were performed. Desmin staining was used as areference concerning identification of degeneration/regeneration and the soleusmuscle was the muscle examined. It was observed that the inflammatory cells, aswell as blood vessel walls in the myositis areas, expressed TNF-alpha mRNA.Muscle fibers that were interpreted to represent necrotic fibers expressedTNF-alpha mRNA reactions and showed NK-1R immunoreactions, the reactions beingconfined to white blood cells that had infiltrated into the fibers. Musclefibers that were interpreted to be in a regenerative state expressedpatchy/widespread TNF-alpha mRNA and point like NK-1R immunoreactions. Abnormalmuscle fibers thus showed TNF-alpha mRNA as well as NK-1R immunoreactions.Normal muscle fibers never showed these reactions. Occurrence of inflammatorycell and muscle fiber TNF-alpha mRNA reactions was equally marked in the myositisareas of the contralateral side as in these areas of the ipsilateralexperimental side. The observations show that the TNF-alpha system is muchinvolved in the processes that occur in the muscle derangement/myositisprocesses. The involvement relates to effects in processes of both regenerationand muscle fiber necrosis. It may be that substance P via activation throughthe NK-1R influences the TNF-alpha expression. The findings of TNF-alphaupregulation also for the contralateral side show that the TNF-alpha system isinvolved both ipsi and contralaterally during the development of myosits/muscleaffection in response to unilateral overuse.