PURPOSE: The purpose of this study was to identify the expression of anti-inflammatory cytokines in various tissues of rat forelimb following repetitive stress. BACKGROUND: Anti-inflammatory cytokines inhibit secretion of pro-inflammatory cytokines, tissue destruction and cell migration and mitosis during acute and chronic inflammatory responses. SUBJECTS: 29 young adult (12-24 weeks of age) Sprague-Dawley rats were used for this study (n=16 experimental and n=13 control). METHODS: Rats were trained to reach and grasp at three repetition-force levels: low repetition, negligible force (LR, NF: 2 reaches per minute, <5% MVC, n=4); high repetition, negligible force (HR, NF: 4 reaches per minute, <5% MVC, n = 8) and high repetition, high force (HR, HF: 4 reaches/minute, 60% MVC, n=4) for 2 hours per day, 3 days per week for up to 12 weeks. Following sacrifice of the rats by lethal overdose of Nembutol, upper extremity musculotendinous tissues were collected, frozen sectioned and probed using antibodies against IL-3, IL-4, IL-6, IL-10 and ED1, an activated macrophage marker. Tissues from the HR, NF group were also examined for IL-10 using SDS-page gel electrophoresis followed by Western blot analysis or ELISA. DATA ANALYSIS: Immunohistochemical results were analyzed descriptively by observation of the probed serial sections. Western blots for controls and 7/8 week HR, NF animals were analyzed by densitometry. IL-10 ELISA results for controls and 7/8 week HR, NF animals were compared by unpaired t-test. RESULTS: In the 12 week HR, NF group, increased immunoexpression of IL-3, IL-6 and IL-10 was noted in endothelial cells, monocytes/macrophages and fibroblasts. Immunoexpression of IL-6 and IL-10 in Schwann cells increased by 12 weeks in the HR, NF group; however, IL-3 immunoexpression decreased by this time point in Schwann cells. IL-4 expression increased only in endothelial cells and macrophages with performance of the LR, NF task for 12 weeks. Only IL3 increased in tissues of the HR, HF group; however, this group performed the task for only 6 weeks. Western blot analysis showed an increase in band density for IL-10 at week 8 in the HR, NF group. Although not statistically significant (p>0.05), ELISA demonstrated an increase of IL-10 by 8 weeks of performance of the HR, NF task. CONCLUSIONS: The increase in anti-inflammatory cytokines indicates that inflammation was induced by these repetitive tasks, and that a repair process has commenced. Whether or not this repair will be successful with continued repetitive task performance is uncertain. FUNDING SOURCES: FPT, NIAMS and NIOSH.

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