期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 41, 期 1, 页码 4-18出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2006.01.027
关键词
cytokines; hyperoxia; lung injury; free radicals; growth factors; newborn; pulmonary; cell death
资金
- NHLBI NIH HHS [HL-56389, HL-74195, HL-61904, HL-64242] Funding Source: Medline
Cytokines are peptides that are produced by virtually every nucleated cell type in the body, possess overlapping biological activities, exert different effects at different concentrations, can either synergize or antagonize the effects of other cytokines, are regulated in a complex manner, and function via cytokine cascades. Hyperoxia-induced acute lung injury (HALT) is characterized by an influx of inflammatory cells, increased pulmonary permeability, and endothelial and epithelial cell injury/death. Some of these effects are orchestrated by cytokines. There are significant differences in the response of the developing versus the adult lung to hyperoxia. We review here cytokines (and select growth factors) that are involved in tolerance toward HALI in animal models. Increased cytokine expression and release have a cascade effect in HALT. IL-1 precedes the increase in IL-6 and CINC-1/IL-8 and this seems to predate the influx of inflammatory cells. Inflammatory cells in the alveolar space amplify the lung damage. Other cytokines that are primarily involved in this inflammatory response include IFN-gamma, MCP-1, and MIP-2. Certain cytokines (and growth factors) seem to ameliorate HALT by affecting cell death pathways. These include GM-CSF, KGF, IL-11, IL-13, and VEGF. There are significant differences in the type and temporal sequence of cytokine expression and release in the adult and newborn lung in response to hyperoxia. The newborn lung is greatly resistant to hyperoxia compared to the adult. The delayed increase in lung IL-1 and IL-6 in the newborn could induce protective factors that would help in the resolution of hyperoxia-induced injury. Designing a therapeutic approach to counteract oxygen toxicity in the adult and immature lung first needs understanding of the unique responses in each scenario. (c) 2006 Elsevier Inc. All rights reserved.
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