Modulation of IL-1 production and IL-1 release during experimental trypanosome infections.

Abstract

Macrophage populations derived from Trypanosoma brucei-infected mice suppress both interleukin-2 (IL-2) production and IL-2 receptor expression. To try to identify the regulatory level by which the T-cell activation is switched off, we have analysed the potential of the suppressive macrophage-like cells to block the secretion of the accessory cell-derived T cell co-stimulator interleukin-1 (IL-1). The IL-1 secretion, however, was found to be greatly increased rather than decreased. The increased secretion was in part caused by an increased release rather than by an increased synthesis. In the presence of an in vitro trigger (lipopolysaccharide), the IL-1 secretion was increased 20-30-fold by the infection whereas the total IL-1 production increased only 1.5-2-fold. Macrophages from infected mice thus manifested a marginally increased IL-1 synthesis but released a markedly larger proportion of the synthesized monokine than normal macrophages. In the absence of an in vitro trigger, the infection caused a 10-15-fold increase in IL-1 synthesis as a consequence of an in vivo preactivation. This increase was only observed when the synthesis of prostaglandins was blocked by addition of indomethacin.