Cytokine expression in the muscle of HIV-infected patients: Evidence for interleukin-1α accumulation in mitochondria of AZT fibers
✍ Scribed by Dr R. K. Gherardi; A. Florea-Strat; G. Fromont; F. Poron; J-C. Sabourin; J. Authier
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- English
- Weight
- 772 KB
- Volume
- 36
- Category
- Article
- ISSN
- 0364-5134
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✦ Synopsis
To evaluate the possible role of cytokines in human immunodeficiency virus (H1V)-associated muscular disorders, we performed immunocytochemistry for interleukin-la, -1 p, and -6 and tumor necrosis factor-@ on frozen muscle biopsy specimens from HIV-infected patients with various myopathies (HIV polymyositis in 5, HIV-wasting syndrome in 5 , tidovudine myopathy in 10) and from seronegative individuals (normal muscle in 2, mitochondrial cytopathies in 10). The HIV-infected patients showed positive reactivities in vessels (interleukin-1) and in inflammatory cells (mainly interleukin-1 and tumor necrosis factor-a), including perivascular hemosiderin-laden macrophages in 5 patients. In zidovudine myopathy, a majority of AZT fibers (i.e., ragged-red fibers with marked myofibrillar changes) showed mild to marked expression of interleukin-1. Expression of interleukin-1 in the other mitochondrial myopathies was much weaker. Interleukin-lp messenger RNA was demonstrated in muscle fibers by in situ hybridization, implying that interleukin-1 was produced in muscle cells. Immunoelectron microscopy showed that interleukin-la was mainly bound to mitochondrial membranes in AZT fibers. Proinflammatory and destructive effects of the studied cytokines might be responsible for several myopathological changes observed in HIV-infected patients, including inflammation and hemosiderin deposits in muscle tissue, and prominent myofibrillar breakdown in AZT fibers.