Late acquisition of hyporesponsiyeness to lipopolysaccharide · by Mycobacterium avium-infected human macrophages in producing tumor necrosis factor-α but not interleukin-1β and -6

To investigate whether infection with Mycobacterium avium modifies the cytokine response of human macrophages (Mφ) to lipopolysaccharide (LPS), the release of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α was determined in infected and uninfected Mφ, unstimulated or stimulated with LPS. In unstimulated Mφ, the release of IL-1β and IL-6 increased with the progress of infection while that of TNF-α progressively decreased. When Mφ were stimulated with LPS, IL-1β and IL-6 levels were always higher in infected than in uninfected cells, but levels of TNF-α significantly decreased in infected Mφ. A similar trend was obtained for TNF-α mRNA expression. Altogether, these results indicate that infected Mφ react to LPS stimulus with enhanced levels of IL-1β and IL-6 but are unable to restore the production of TNF-α impaired by the growth of the intracellular mycobacteria.