Résumé :
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Communication n° 398 Macrophagic myofasciitis (MMF) is a specific histopathologic lesion, characterized by accumulations of both MHC-1 antigen-expressing macrophages and CD8+T-cells in muscle and fascia. MMF assesses persistence of aluminum hydroxide [Al(OH)3], a potent Th2 adjuvant, within antigen presenting cells at site of previous intra-muscular (i.m.) injection. Both Al(OH)3 pharmacokinetics and basis of individual susceptibility to develop long-lasting MMF are largely unknown. We experimentally evaluated the local residence time of Al(OH)3-loaded macrophages and the role of T-cells in their clearance from muscle. I.m. injections of 10 µL of an Al(OH)3-adjuvanted vaccine were performed in Sprague-Dawley rats with balanced Th1/Th2 immunity, and Lewis rats with Th1-biased immunity. Evaluation included myopathological study of vaccine-induced MMF-like lesions, morphometric analysis of lesion volume, and circulating cytokines determination. In both strains, macrophagic infiltrates were detected in the injected muscle up to 12 months after injection, with progressive shrinkage and T-cell enrichment of lesions. Lewis rats had significantly smaller lesions (p< 0.05) and lower levels of IL-6 (p<0.01) and IL-2 (p<0.04) than Sprague-Dawley rats. Conclusion: (i) Al(OH)3 may persist up to one year in muscle; (ii) the genetic background may influence size of lesions; (iii) weak cytotoxic T-cell responses may represent a susceptibility factor for MMF.
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