No abstract

Women are conferred with greater immunologic and survival benefits compared to men. Female sex steroids contribute to this sexual dimorphism. Furthermore, during human pregnancy when female sex hormones are elevated, neutrophil apoptosis is delayed. This study examines the specific effects of estradiol and progesterone on neutrophil apoptosis and function in healthy adult men and women. We also examined the contribution of these hormones to the persistence and resolution of an inflammatory response. Spontaneous apoptosis was significantly decreased in women compared with men. Physiologic doses of estradiol and progesterone caused a further delay in spontaneous apoptosis in both men and women but did not diminish Fas antibodyinduced apoptosis. The delay in apoptosis was mediated at the level of the mitochondria with decreased release of cytochrome c, which may alter caspase cleavage and activity. There were no associated alterations in neutrophil CD11b, but production of reactive oxygen intermediates (ROIs) in women was increased. Thus, female sex hormones mediate delayed neutrophil apoptosis in both sexes and enhance female intracellular production of ROIs. Modulating hormonal responses may be an effective therapeutic tool in combating inflammatory diseases. IntroductionFrom conception to senescence, women have a significant survival advantage. 1 Men are more susceptible to sepsis and subsequent morbidity and mortality than women of reproductive age. [2][3][4] The incidence of sepsis in postmenopausal women increases to levels almost equal to those seen in age-matched men. 5,6 The exact mechanism mediating this sexual dimorphism is unclear. However, female sex hormones have been implicated because they modulate the immune system under normal and stress conditions. 7 Following trauma or hemorrhage, female mice maintain their immune function, whereas male mice have significantly depressed responses. 8 Estradiol has been shown to be protective in organ ischemia-reperfusion injury and shock by preventing androgeninduced immunosuppression in male animals. 9-12 Thus, female sex hormones may be a useful adjunct in preventing trauma-induced immunosuppression and the associated increased susceptibility to sepsis. 13 Estrogen treatment, testosterone depletion, and testosterone receptor antagonists improve outcome in male animals following trauma and sepsis. 14 The exact role of changes in the estradiol-testosterone ratio in immune function requires further clarification. Estrogens are also cited as having a protective role in neurodegenerative and cardiac diseases through a variety of mechanisms including blockade of oxidation, antagonism of nitric oxide synthase activity, 15 and interference with the apoptotic process in a variety of cell systems.Altered neutrophil apoptosis has been implicated in the pathogenesis of several inflammatory conditions. 16,17 Excessively delayed neutrophil apoptosis is associated with the systemic inflammatory response syndrome (SIRS). This syndrome is also characterized by activated neutro...

The WHO (2001) recommends exclusive breast-feeding and delaying the introduction of solid foods to an infant's diet until 6 months postpartum. However, in many countries, this recommendation is followed by few mothers, and earlier weaning onto solids is a commonly reported global practice. Therefore, this prospective, observational study aimed to assess compliance with the WHO recommendation and examine weaning practices, including the timing of weaning of infants, and to investigate the factors that predict weaning at # 12 weeks. From an initial sample of 539 pregnant women recruited from the Coombe Women and Infants University Hospital, Dublin, 401 eligible mothers were followed up at 6 weeks and 6 months postpartum. Quantitative data were obtained on mothers' weaning practices using semi-structured questionnaires and a short dietary history of the infant's usual diet at 6 months. Only one mother (0·2 %) complied with the WHO recommendation to exclusively breastfeed up to 6 months. Ninety-one (22·6 %) infants were prematurely weaned onto solids at # 12 weeks with predictive factors after adjustment, including mothers' antenatal reporting that infants should be weaned onto solids at #12 weeks, formula feeding at 12 weeks and mothers' reporting of the maternal grandmother as the principal source of advice on infant feeding. Mothers who weaned their infants at # 12 weeks were more likely to engage in other sub-optimal weaning practices, including the addition of non-recommended condiments to their infants' foods. Provision of professional advice and exploring antenatal maternal misperceptions are potential areas for targeted interventions to improve compliance with the recommended weaning practices.