In Situ Production of Gamma Interferon, Interleukin-4, and Tumor Necrosis Factor Alpha mRNA in Human Lung Tuberculous Granulomas

AUTOR(ES)

Fenhalls, Gael

FONTE

American Society for Microbiology

RESUMO

Human tuberculous granulomas from five adults undergoing surgery for hemoptysis were analyzed by nonradioactive in situ hybridization for tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), and interleukin-4 (IL-4) gene expression. All of the patients produced TNF-α mRNA. Three patients stained positive for both IFN-γ and IL-4 mRNA; the other two stained positive for IFN-γ but not IL-4 mRNA. Heterogeneity between the granulomas was observed in those patients staining positive for both IFN-γ and IL-4 mRNA; these patients exhibited granulomas having IFN-γ and not IL-4 mRNA as well as granulomas positive for both cytokine mRNAs. There was no evidence of caseation in these granulomas, and the cytokine patterns may represent events in the evolution of the granuloma. However, in those granulomas exhibiting caseous necrosis, very little IFN-γ or IL-4 mRNA was observed, implying that progression of the granuloma is accompanied by a down regulation of T-cell responses. TNF-α mRNA expression was highest in patients with both IFN-γ and IL-4 mRNA. Populations of CD68 positive macrophage-like cells within the granulomas produce mRNA for TNF-α, IFN-γ, and IL-4. This implies that macrophages within the tuberculous granuloma may not be dependent on T-cell cytokines for modulation of their function but may be able to regulate their own activation state and that of the surrounding T cells. These findings have implications on the delivery of immunotherapies to patients with tuberculosis.

Documentos Relacionados

• Activation of tuberculostatic macrophage functions by gamma interferon, interleukin-4, and tumor necrosis factor.
• In vivo regulation of nitric oxide production by tumor necrosis factor alpha and gamma interferon, but not by interleukin-4, during blood stage malaria in mice.
• Development of Francisella tularensis antigen responses measured as T-lymphocyte proliferation and cytokine production (tumor necrosis factor alpha, gamma interferon, and interleukin-2 and -4) during human tularemia.
• Lipopolysaccharide and monophosphoryl lipid A differentially regulate interleukin-12, gamma interferon, and interleukin-10 mRNA production in murine macrophages.
• Endogenous gamma interferon, tumor necrosis factor, and interleukin-6 in Staphylococcus aureus infection in mice.