Immunology
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Immunologically immature neonates suffer the highest incidence of paediatric sepsis. Postnatal immunological maturation is characterized by a relatively hypo-inflammatory immune response. ⋯ Immunological maturational differences likely affect the neonate's ability to mount an appropriate hyper-inflammatory response, a counteractive hypo-inflammatory response, and subsequent return to immune system homeostasis. To better understand the role of the hypo-inflammatory response in paediatric sepsis, we will explore the maturation of the immune system and the effect it may have on the sepsis-induced hypo-inflammatory response.
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A decrease in the number of dendritic cells (DCs) is a major cause of post-sepsis immunosuppression and opportunistic infection and is closely associated with poor prognosis. Increasing the number of DCs to replenish their numbers post sepsis can improve the condition. This therapeutic approach could improve recovery after sepsis. ⋯ BMDC transfer resulted in the following changes: a significant reduction in damage to the liver, kidney and pancreas in the CLP-septic mice as well as in the pathological changes seen in the liver, lung, small intestine and pancreas; significantly elevated levels of the T helper type 1 (Th1) cytokines IFN-γ and IL-12p70 in the serum; decreased levels of the Th2 cytokines IL-6 and IL-10 in the serum; reduced expression of PD-1 molecules on CD4(+) T cells; reduced the proliferation and differentiation of splenic suppressor T cells and CD4(+) CD25(+) Foxp3(+) regulatory T cells, and a significant increase in the survival rate of the septic animals. These results show that administration of BMDCs may have modulated the differentiation and immune function of T cells and contributed to alleviate immunosuppression, hence reducing organ damage and mortality post sepsis. Hence, the immunoregulatory effect of BMDC treatment has potential for the treatment of sepsis.