Regulation of Il-10 Secretion After Phagocytosis of mycobacterium Tuberculosis by Human Monocytic Cells

Author： Shaw T.C. Thomas L.H. Friedland J.S.

ISSN： 1043-4666

Source： Cytokine, Vol.12, Iss.5, 2000-05, pp. : 483-486

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Abstract

Downregulation of pro-inflammatory events in the immune response to Mycobacterium tuberculosisis critical to prevent host tissue injury. Interleukin (IL-)10 is an important anti-inflammatory cytokine secreted in human tuberculosis but little is known about the control of such IL-10 release. Using an established cellular model, we measured IL-10 secretion after phagocytosis of M. tuberculosis. Phagocytosis of M. tuberculosis but not of inert latex beads by human monocytic (THP-1) cells resulted in IL-10 secretion maximal at 24 h. The magnitude and kinetics of IL-10 secretion were distinct from IL-10 secretion after phagocytosis of yeast-derived zymosan and depended on transcriptional activity and protein synthesis in infected monocytes. IL-10 secretion was decreased in a dose-dependent manner by specific inhibitors of tyrosine kinases, protein kinase (PK) C and PKA. Inhibition of more than one pathway did not result in further synergistic or additive reduction in IL-10 secretion. Finally, specific neutralising antibody directed against IL-10 demonstrated that IL-10 secreted by infected monocytic cells did not block autologous IL-8 secretion.