REGULATION OF INTERLEUKIN-10 GENE-EXPRESSION - POSSIBLE MECHANISMS ACCOUNTING FOR ITS UP-REGULATION AND FOR MATURATIONAL DIFFERENCES IN ITSEXPRESSION BY BLOOD MONONUCLEAR-CELLS

Interleukin-10 (IL-10) downmodulates phagocytic immune responses and a ccentuates humoral responses. Human neonates exhibit broad immune defi cits that parallel actions of IL-10, We postulated that IL-10 producti on would be diminished in neonatal blood cells, We found that IL-10 pr oduction by lipopolysaccharide-stimulated peripheral blood mononuclear cells (PBMNCs) in vitro was greater by adult cells than by term cells and preterm cells, Additional studies were undertaken to identify mec hanisms responsible for the developmental differences in IL-10 gene ex pression. IL-10 transcription was present in freshly isolated adult an d neonatal cells in the absence of detectable levels of transcript. Tr anscription rates were not different between adult and neonatal cells. IL-10 transcripts were approximately 40% more abundant in adult cells than in term cells and were consistent with differences in secreted p rotein; however, no differences were noted in mRNA stability. IL-10 ha lf-life was 60 minutes for both adult and term PBMNCs, We conclude tha t up-regulation of IL-10 gene expression in PBMNCs is modulated at the post-transcriptional level, that IL-10 protein production and mRNA co ntent are greater in activated cells from adults compared with those f rom neonates, and that maturational differences in IL-10 expression ar e not due to differences in transcription rate or mRNA stability, Matu rational differences in IL-10 expression might be due to differences i n subpopulations of cytokine-producing cells or differences in nucleo- cytoplasmic transport. (C) 1997 by The American Society of Hematology.