Down-modulation of mycobacterial-induced IL-1β production in human mononuclear cells by IL-4 |
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| Authors: | P M NDEZ-SAMPERIO, M HERNANDEZ-GARAY, A BADILLO-FLORES, A NU
EZ-VAZQUEZ |
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| Affiliation: | P MÉNDEZ-SAMPERIO, M HERNANDEZ-GARAY, A BADILLO-FLORES, and A NUÑEZ-VAZQUEZ |
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| Abstract: | Tuberculosis is characterized by a cellular immune response mediated by various cytokines, including IL-1β released by stimulated mononuclear cells. It is now well established that IL-1β plays an important role in local and systemic inflammatory response in tuberculosis. Here we have demonstrated, for the first time, that addition of IL-4 to human mononuclear cells obtained from 11 healthy bacille Calmette–Guérin (BCG)-vaccinated donors reduced BCG-induced production of IL-1β by 91.46 ± 2.2%. This inhibitory effect was found highly significant (P < 0.001) and was dose-dependent. The effect of IL-4 on the secretion of IL-1β was specific, since a complete reversion was obtained with a neutralizing MoAb to human IL-4. In addition, this inhibitory effect was not attributed to a cytotoxic effect, since trypan blue exclusion studies indicated no loss of cell viability in response to IL-4. Interestingly, the induction of IL-1β was regulated by IL-4, at least in part, by a direct mechanism mediated through the 130 extracellular domain of the IL-4 receptor, as demonstrated by incubation of the mononuclear cells with the neutralizing anti-IL-4 receptor MoAb. Finally, a significant down-regulation of IL-1β secretion was observed in hsp70-stimulated mononuclear cells cultured with IL-4. Further experimental work is needed to establish the relevance of IL-4 in human mycobacterial infection in vivo. However, an understanding of the mechanisms that control IL-1β secretion in human mycobacterial infections is essential to understand the pathogenesis of tuberculosis. |
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| Keywords: | heat shock protein IL-1 IL-4 mycobacteria tuberculosis |
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