Late acquisition of hyporesponsiveness to lipopolysaccharide by Mycobacterium avium-infected human macrophages in producing tumor necrosis factor-alpha but not interleukin-1 beta and -6.
To investigate whether infection with Mycobacterium avium modifies the cytokine response of human macrophages (Mphi) to lipopolysaccharide (LPS), the release of interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha was determined in infected and uninfected Mphi, unstimulated or stimulated with LPS. In unstimulated Mphi, the release of IL-1 beta and IL-6 increased with the progress of infection while that of TNF-alpha progressively decreased. When Mphi were stimulated with LPS, IL-1 beta and IL-6 levels were always higher in infected than in uninfected cells, but levels of TNF-alpha significantly decreased in infected Mphi. A similar trend was obtained for TNF-alpha mRNA expression. Altogether, these results indicate that infected Mphi react to LPS stimulus with enhanced levels of IL-1 beta and IL-6 but are unable to restore the production of TNF-alpha impaired by the growth of the intracellular mycobacteria.
Fattorini
L
L
Laboratory of Bacteriology and Medical Mycology, Istituto Superiore di Sanitá, Rome, Italy.
Xiao
Y
Y
Ausiello
C M
CM
Urbani
F
F
laSala
A
A
Mattei
M
M
Orefici
G
G
D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000382:microbiology / Q000502:physiology*; D015269:Mycobacterium avium Complex / Q000254:growth & development / Q000276:immunology*; D015270:Mycobacterium avium-intracellulare Infection / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha