Altered IL-1 expression and compartmentalization in monocytes from patients with AIDS stimulated with Mycobacterium avium complex

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-α 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-1α and IL-1β release in AIDS patients than HS (P <0.05). The ratio of cell-associated to supernatant IL-1α also was increased in AIDS patients (P = 0.03). IL-1β mRNA expression paralleled protein release in either group of subjects. In both HS and AIDS patients, stimulation with Stud induced more IL- 1 and TNF-α release by monocytes compared to SmT. In AIDS patients, Stud 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.