Inflammatory mediators in perinatal asphyxia and infection.

Inflammatory mediators produced in response to hypoxic-ischemic (H-I) injury and infection in the newborn, include multi-potent cytokines and chemokines released by a variety of somatic and bone marrow-derived cells both locally, in the brain and systemically, in the circulation. Pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6, IL-18, interferon (IFN)-γ and tumor necrosis factor (TNF)-α, are small polypeptides secreted in response to cellular injury and inflammation. Cytokines trigger somatic and immune cell activation, differentiation and death after signaling through their cognate receptors. Chemokines, such as CCL2 and CXCL8, are chemotactic cytokines that induce cells of the innate and adaptive immune system to leave the blood stream and migrate to sites of injury in the central nervous system (CNS) and in the periphery [1]. Cytokines and chemokines are considered critical mediators of brain damage and clinical indicators of overwhelming sepsis in the newborns. We review the cellular origin and role of cytokines and chemokines in these diseases. We also discuss treatment modalities that may interrupt these inflammatory cascades. A better understanding of the role of cytokines and chemokines in response to H-I injury and infection is likely to improve the outcome and long-term prognosis of these diseases in the newborn period.