Cytokine expression in the muscle of HIV‐infected patients: Evidence for interleukin‐1α accumulation in mitochondria of AZT fibers

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Abstract
To evaluate the possible role of cytokines in human immunodeficiency virus (HIV)–associated muscular disorders, we performed immunocytochemistry for interleukin‐1α, ‐1β, and ‐6 and tumor necrosis factor‐α on frozen muscle biopsy specimens from HIV‐infected patients with various myopathies (HIV polymyositis in 5, HIV‐wasting syndrome in 5, zidovudine 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‐α), 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‐1β 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‐1α 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.