A new feature of importance for the TNF-alpha system in inflammation—Bilateral myositis that develops early in response to unilateral overuse shows a marked involvement of TNF-alpha not only in the exercised side but also contralaterally

Abstract

Using a rabbit model leading to myositis in response to exercise-induced muscle overuse, we have previously observed that TNF-alpha is involved in the exercised muscle in early developing myositis as well as both ipsiand contralaterally in the myositis which develops in response to a lengthened period of overuse. It is unknown if TNF-alpha can also be engaged contralaterally in early stages of myositis. The hypothesis was that this is the case. It was therefore evaluated whether the TNF-alpha system is early involved contralaterally. An experimental model of 1 week of overuse of the soleus muscle on one side leading to myositis was used, and in situ hybridization and immunohistochemistry were applied to study the expression patterns of TNF-alpha in the soleus muscle in the contralateral side. TNF-alpha was expressed in the myositis process which occurred contralaterally. There were thus TNF-alpha mRNA reactions in the cells of the inflammatory infiltrates, in blood vessel walls and in certain of the muscle fibers. Parts of the latter were necrotic fibers, whereas others were interpreted to be in a regenerative stage. TNF-alpha immunoreactions were seen for infiltrating white blood cells. The observations show that the TNF-alpha system is early involved in the cross-over effects that occur in response to unilateral muscle overuse leading to myositis bilaterally. TNF-alpha is likely to have pro-inflammatory and destructive effects but also to have effects in the muscle regenerative processes. The occurrence of an early involvement of the TNF-alpha system contralaterally to the injury side shows a new aspect of importance of this system in inflammation.