CYTOKINE EXPRESSION IN THE MUSCLE OF HIV-INFECTED PATIENTS - EVIDENCEFOR INTERLEUKIN-1-ALPHA ACCUMULATION IN MITOCHONDRIA OF AZT FIBERS

To evaluate the possible role of cytokines in human immunodeficiency v irus (HIV)-associated muscular disorders, we performed immunocytochemi stry for interleukin-1 alpha, -1 beta, and -6 and tumor necrosis facto r-a on frozen muscle biopsy specimens from HIV-infected patients with various myopathies (HIV polymyositis in 5, HIV-wasting syndrome in 5, zidovudine myopathy in LO) and from seronegative individuals (normal m uscle in 2, mitochondrial cytopathies in 10). The HIV-infected patient s showed positive reactivities in vessels (interleukin-1) and in infla mmatory cells (mainly interleukin-1 and tumor necrosis factor-alpha), including perivascular hemosiderin-laden macrophages in 5 patients. In zidovudine myopathy, a majority of AZT fibers (i.e., ragged-red fiber s with marked myofibrillar changes) showed mild to marked expression o f Interleukin-1. Expression of interleukin-1 in the other mitochondria l myopathies was much weaker. Interleukin-1 beta messenger RNA was dem onstrated in muscle fibers by in situ hybridization, implying that int erleukin-l was produced in muscle cells. Immunoelectron microscopy sho wed that interleukin-1 alpha was mainly bound to mitochondrial membran es in AZT fibers. Proinflammatory and destructive effects of the studi ed cytokines might be responsible for several myopathological changes observed in HIV-infected patients, including inflammation and hemoside rin deposits in muscle tissue, and prominent myofibrillar breakdown in AZT fibers.