Supernatants derived from CD8+ lymphocytes activated by mycobacterial fractions inhibit cytokine production. The role of interleukin-6.
Our study examined the effects of supernatants derived from CD8+ lymphocytes treated with high molecular weight components of Mycobacterium tuberculosis on cytokine production. Such suppressor but not control supernatants increased the production of IL-4 and IL-6 whilst suppressing IL-1 beta, TNF-alpha, IL-2 and IFN-gamma production by monocytes and lymphocytes. The effects on cytokine production were time dependent being observed as early as 4 hours with peak activity observed at 24 hours. The inhibition of IL-1 beta and TNF-alpha by monocytes appeared to be related to increases in IL-6 levels present in supernatants of non-adherent lymphocytes incubated with mycobacterial components. This was confirmed by studies demonstrating that the addition of recombinant IL-6 to cultures depressed the production of these cytokines. Furthermore the addition of monoclonal anti-IL6 to such cultures restored the production of IL-1 beta and TNF-alpha. The results suggest that mycobacterial components inhibit host cellular functions by manipulating the host's cytokine network.
Sussman
G
G
Department of Immunology, School of Pathology, University of Witwatersrand, Johannesburg, Republic of South Africa.
Wadee
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AA
D000942:Antigens, Bacterial / Q000276:immunology* / Q000302:isolation & purification; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003864:Depression, Chemical; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry* / Q000187:drug effects
D000942:Antigens, Bacterial; D016207:Cytokines; D015850:Interleukin-6; D011994:Recombinant Proteins; D015847:Interleukin-4