Down-modulation of mycobacterial-induced IL-1 beta production in human mononuclear cells by IL-4.
Tuberculosis is characterized by a cellular immune response mediated by various cytokines, including IL-1 beta released by stimulated mononuclear cells. It is now well established that IL-I beta plays an important role in local and systemic inflammatory response in tuberculosis. Here we have demonstrated, for the first time, that addition to IL-4 to human mononuclear cells obtained from 11 healthy bacille Calmette-Guérin (BCG)-vaccinated donors reduced BCG-induced production of IL-1 beta by 91.46 +/- 2.2%. This inhibitory effect was found highly significant (P less than 0.001) and was dose-dependent. The effect of IL-4 on the secretion of IL-1 beta 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-1 beta was regulated by IL-4, at least in part, by direct mechanism mediated through the extracellular domain of the 130-kD 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-1 beta 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-1 beta secretion in human mycobacterial infections is essential to understand the pathogenesis of tuberculosis.
Méndez-Samperio
P
P
Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Mexico.
Hernandez-Garay
M
M
Badillo-Flores
A
A
Nuñez-Vazquez
A
A
D018840:HSP70 Heat-Shock Proteins / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism* / Q000382:microbiology; D009163:Mycobacterium bovis / Q000276:immunology / Q000502:physiology*
D018840:HSP70 Heat-Shock Proteins; D007375:Interleukin-1; D015847:Interleukin-4