IN-VITRO CYTOKINE PRODUCTION AND PHENOTYPE EXPRESSION BY BLOOD MONONUCLEAR-CELLS FROM UMBILICAL CORDS, CHILDREN AND ADULTS

Age related differences in immunological reactions include variations in the in vitro functions of blood mononuclear cells (MNC). In an atte mpt to understand the mechanism behind these differences we examined a ge related differences in the phenotype profiles of MNC in parallel wi th the in vitro production of interleukin IL-6, tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFNg) in neonates, children a nd adults. In cultures without added polyclonal activators IL-6 and TN F alpha levels in children were 3-6 times higher than those of umbilic al cords and adults. However, using optimal in vitro stimulation (E. c oil lipopolysaccharide (LPS), phytohaemmagglutinin or pokeweed mitogen (PWM)) no significant differences in the levels of these cytokines we re observed. The levels of IFNg in PWM driven cultures followed a diff erent pattern with comparable levels in children and adults, and unmea surable levels in cord blood MNC. Flow cytometry analysis of the pheno typic distribution of MNC revealed age related differences in the expr ession of CD3, CD4, CD8, CD14, CD19, CD45RA, CD45R0, CD2, LFA-1, ICAM- 1 and LFA-3. Correlation studies did not indicate that the observed di fferences in cytokine production could be ascribed to differences in t he frequency of monocytes, T cells or B cells. The TNF alpha levels in suboptimally stimulated cultures correlated negatively with the expre ssion of LFA-3 and positively with CD45RA, while IFNg correlated posit ively with CD2, LFA-1, CD45R0 and CD8. In conclusion, the study provid es evidence of age related differences in the production of TNF alpha, IL-6 and IFNg among neonates, children and adults. These differences may to some extent be caused by differences in the expression of cell surface molecules involved in cellular interactions and signalling.