Production of Interleukin-1alpha and Tumor Necrosis Factor-alpha by Human Cord and Adult Blood Mononuclear Cells Stimulated by TSST-1 and LPS

Park, Eun Ae; Kim, Kyung Hyo; Kim, Gyoung Hee

Abstract

PURPOSE: Immature immunological defens mechanism in the neonate may contribute to the high susceptibility to overwhelming sepsis. S. aureus TSST-1 and E. coli LPS known as one of the important pathogens of septic shock or toxic shock induce massive release of various cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1alpha (IL-1alpha) produced from peripheral blood mononuclear cells (PBMC). In contrast, limited information has been provided so far concerning the capacity of cytokine production from neonatal immune cells.
METHODS
This study was conducted to compare the secretion of proinflammatory cytokines, such as IL-l and TNF-alpha from cord blood PBMC to those from adult blood PBMC stimulated by S. aureus TSST-1 and E. coli LPS.
RESULTS
1) IL 1-alpha was secreted in a time-dependent manner from cord & adult blood PBMC stimulated with several cytokine inducers, and LPS stimulated adult & cord blood PBMC secreted IL 1-alpha in a dose-dependent manner. 2) TNF-alpha secretion from cord blood PBMC stimulated with LPS and IFN- significantly decreased in a time dependent manner, but not from adult PBMC. And secretion of TNF- from cord blood PBMC reached the highest level 24 hours after stimulated with LPS or IFN-gamma. The secretion of TNF-alpha from adult blood PBMC showed similar pattern to those from cord blood PBMC, but higher than cord blood PBMC. 3) IL-1alpha & TNF-alpha secretion from cord & adult blood PBMC stimulated with TSST-1 had no significant difference except in TNF- secretion by TSST-1 at 96 hours. 4) The secretion of IL-1alpha from adult PBMC stimulated with LPS showed higher and longer than that from cord blood PBMC. 5) IL-1alpha & TNF-alpha secretion from cord & adult blood PBMC stimulated with IFN-gamma had no significant difference.
CONCLUSIONS
In summary, proinflammatory cytokines such as IL-1alpha, TNF-alpha in cord blood PBMC were secreted in a time dependent manner, but the amounts of IL-1alpha and TNF-alpha secretion were lesser than those of adult blood PBMC, especially stimulated by LPS. These results suggest that increased susceptibility to infection in neonatal period may be partially from a functional immaturity of cord blood mononuclear cells.