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Published on: October 16, 2013
Altered IL-1 expression and compartmentalization in monocytes from patients with AIDS stimulated with Mycobacterium
J L Johnson1, H Shiratsuchi, Z Toossi
1Department of Medicine, Case Western Reserve University, University Hospitals, Cleveland, Ohio, USA.
Abstract:
The pathophysiologic basis for the exuberant intracellular growth of Mycobacterium avium complex (MAC) in AIDS patients is unclear but may relate to altered expression of modulatory cytokines. Interleukin (IL)-1, IL-6, and TNF-alpha expression by monocytes from AIDS patients and healthy subjects (HS) stimulated with isogeneic MAC strains (SmT, smooth-transparent, virulent; SmD, smooth-domed, avirulent) was examined. Spontaneous cytokine production was not observed in patients with AIDS. MAC strains induced less IL-1 alpha and IL-1 beta release in AIDS patients than HS (P < 0.05). The ratio of cell-associated to supernatant IL-1 alpha also was increased in AIDS patients (P = 0.03). IL-1 beta mRNA expression paralleled protein release in either group of subjects. In both HS and AIDS patients, stimulation with SmD induced more IL-1 and TNF-alpha release by monocytes compared to SmT. In AIDS patients, SmD also induced greater IL-6 release than SmT (P < 0.01). Alterations in monocyte expression and compartmentalization of the regulatory cytokines IL-1 and IL-6 may enhance bacterial replication and contribute to the pathogenesis of MAC infection in AIDS.
