Supernatants derived from CD8+ lymphocytes activated by mycobacterial fractions inhibit cytokine production. The role of interleukin-6

Abstract

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.

Suppression of cytokine production by supernatants from CD8+ lymphocytes activated by mycobacterial fractions: The role of interleukins 4 and 6

“…Decreases in the levels of the latter cytokines appeared to be related to increased levels of IL-6. Since these studies also demonstrated an increase in the levels of IL-4 and because evidence had previously been presented suggesting that IL-4 exerted a suppressor effect on the production of IL-1, IL-2, IL-6, TNFa and IFN--7 [33][34][35][36] the present study extended our previous investigations [28] to examine the production and effect of IL-4 and IL-6 on the production of other cytokines in the presence of supernatants from MN cells pulsed with high molecular weight mycobacterial fractions.…”

“…We had previously demonstrated that supernatants containing suppressor molecules increased the production of IL-4 and IL-6 by MN cells incubated with LPS [28]. The current studies extended these observations by utilising carbohydrates from the previously described glycolipids present in suppressor supernatants [28].…”

“…More recently we have demonstrated that fractionation on sizing columns resulted in activation of CD8 + cells by such high molecular weight fractions. Such artificial fractionation did not require any further processing by macrophages [28].…”

“…We had previously demonstrated that adherent cells infected with mycobacteria release suppressor cell activating factors (SCAF) that induce suppressor lymphocytes to inhibit lymphocyte proliferation and lymphokine production [23][24][25][26][27][28]. Other workers have also suggested that suppressor T cells generated in response to BCG infection inhibit Con A-stimulated T cells from producing IL-2 [7,29].…”

“…Other cytokines affected by mycobacteria or mycobacterial constituents include the inhibition of TNF-c~ [30,31] and IFN--,y [32] production. We had previously reported that supernatants derived from CD8 + lymphocytes treated with mycobacterial components increased the production of IL-4 and IL-6 whilst suppressing IL-1/3, TNF-c~, IL-2 and IFN--7 production by monocytes and lymphocytes [28]. Decreases in the levels of the latter cytokines appeared to be related to increased levels of IL-6.…”