Regulation of Interleukin-8 by Interleukin-10 and Transforming Growth Factor β in Human Monocytes Infected withMycobacterium bovis

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Abstract
Recent studies indicate that interleukin 8 (IL-8) production contributes to the host immune responses against mycobacterial infection. In this study, we were interested to determine whether induction of IL-8 in human monocytes infected withMycobacterium boviswas regulated by other monocyte-derived cytokines important in antimycobacterial immunity: IL-10 and transforming growth factor β (TGF-β). Here, we report that IL-10 reduced, in a graded and significant manner, IL-8 production byM. bovis-infected human monocytes. Additionally, the specificity of the observed inhibition was further confirmed, since the addition of an anti-IL-10 neutralizing antibody completely reversed the inhibitory effect. In contrast, addition or neutralization of TGF-β appeared to have no significant effect onM. bovis-induced IL-8 secretion by human monocytes, whereas CD40 expression onM. bovis-infected monocytes was significantly inhibited by this cytokine. This was consistent with the finding by the reverse transcription-PCR method that pretreatment with IL-10, but not TGF-β, potently inhibited IL-8 mRNA levels. Interestingly, neutralization of endogenous IL-10 did not significantly alter IL-8 secretion, suggesting that induction of IL-8 was not significantly affected by coexpression of IL-10 during infection of human monocytes withM. bovis.Collectively, these data indicate that IL-8 production may be regulated when human monocytes are exposed to IL-10 prior to activation withM. bovisBCG. These data will aid in our understanding of the mechanisms involved in regulating the protective immune response to stimulation withM. bovisBCG.