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अमूर्त

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

Lina Renström, Yafeng Song, Per S Stål and Sture Forsgren

TNF-alpha is known to be involved in muscle damage and inflammation (myositis). The relationships between the TNF-alpha system and muscle fiber necrosis/regeneration and the tachykinin system in this situation are unclear. We have an experimental rabbit model related to unilateral muscle overuse which leads to marked muscle derangement and myositis bilaterally. Using this model, staining for TNF-alpha, in parallel with staining for the substance P-preferred receptor (NK-1R) and desmin were performed. Desmin staining was used as a reference concerning identification of degeneration/regeneration and the soleus muscle was the muscle examined. It was observed that the inflammatory cells, as well as blood vessel walls in the myositis areas, expressed TNF-alpha mRNA. Muscle fibers that were interpreted to represent necrotic fibers expressed TNF-alpha mRNA reactions and showed NK-1R immunoreactions, the reactions being confined to white blood cells that had infiltrated into the fibers. Muscle fibers that were interpreted to be in a regenerative state expressed patchy/widespread TNF-alpha mRNA and point like NK-1R immunoreactions. Abnormal muscle fibers thus showed TNF-alpha mRNA as well as NK-1R immunoreactions. Normal muscle fibers never showed these reactions. Occurrence of inflammatory cell and muscle fiber TNF-alpha mRNA reactions was equally marked in the myositis areas of the contralateral side as in these areas of the ipsilateral experimental side. The observations show that the TNF-alpha system is much involved in the processes that occur in the muscle derangement/myositis processes. The involvement relates to effects in processes of both regeneration and muscle fiber necrosis. It may be that substance P via activation through the NK-1R influences the TNF-alpha expression. The findings of TNF-alpha upregulation also for the contralateral side show that the TNF-alpha system is involved both ipsi and contralaterally during the development of myosits/muscle affection in response to unilateral overuse.