Basis and implications of selectively diminished cytokine production in neonatal susceptibility to infection

Abstract

The human neonate is unduly susceptible to infection with viruses and other pathogens, such as Toxoplasma and Listeria, that survive and replicate within cells. Cellular immunity is the major mechanism of host defense against these intracellular pathogens. Selective immaturity in certain functions of T lymphocytes appears to be a major factor in the neonate's susceptibility to these infections. Particularly striking is the deficiency in production of interferon-gamma. We review the data regarding the deficiency in the production of interferon-gamma by cells of healthy and infected neonates, discuss what is known regarding the cellular and molecular mechanisms for this deficiency, and review the unique role played by interferon-gamma in host defense against intracellular pathogens. The response of the neonate's effector cells to the immunoenhancing effects of interferon-gamma appears to be variable; diminished enhancement by interferon-gamma of cytotoxic cell function and the production of tumor necrosis factor by macrophages may further compound the effects of diminished production of interferon-gamma.