Dysregulation of lymphokine production in the neonate and its impact on neonatal cell mediated immunity.

Haematopoiesis and immune functions in cord blood (CB) are developmentally immature when compared with adult peripheral blood (APB). The defects in CB immune function and cytokine production may both contribute to the immaturity of CB immunity. We have studied the mechanisms associated with the dysregulation of myeloid lineage cytokines, GM-CSF and M-CSF, and lymphokines, IL-12, and IL-15 in activated CB when compared with APB MNC. Furthermore, we have studied the effects of IL-12 and IL-15 on induction of IFN-gamma and TNF-alpha production, NK, and LAK activities in CB and APB. GM-CSF, M-CSF, IL-12 and IL-15 protein and mRNA are decreased in activated CB MNC. These discrepancies are secondary, at least in part, to the altered post-transcriptional regulation. The impaired ability of CB to produce IL-12 and IL-15 in response to stimulation may contribute to the decrease in IFN-gamma, TNF-alpha production, NK and LAK activities. Furthermore, combination of low dose IL-12 and IL-15 may augment cytotoxic activities and minimize toxicity. These findings suggest that reduced cytokine expression from activated CB may contribute to the impaired CB cellular immunity and exogenous lymphokines may compensate for the immaturity in CB.