Females with sepsis have a better prognosis than males, while those of both genders with cirrhosis have a high mortality. Impaired immunity accompanies liver cirrhosis. The potential association between sex and immunologic response of cirrhotic rats in sepsis following immunonutrition was investigated. One hundred and forty-three rats were randomly divided into groups. Liver cirrhosis was produced by weekly feeding of CCl₄ for 8 weeks. Among them, 24 male and 19 female underwent castration one month before studying. The rats were fed with either immune enhancing diet or control diet for five days, then sepsis was induced with cecal ligation and two holes puncture. Main outcomes included mortality and serum cytokines (IL-1β, 6, and 10). Comparisons were made both within and between genders. Cirrhotic non-castrated male rats showed a significant decrease in mortality (64.1% vs. 32.1%, p = 0.032) with better survival than control diet following immune enhancing diet. Lower mortality of cirrhotic non-castrated female rats was found after immune enhancing diet (69.6% vs. 52.1%, p = 0.365). Cirrhotic castrated male rats showed a lower mortality (44.4%) following immune enhancing diet, and cirrhotic castrated female rats also showed significantly lower mortality and better survival than control diet after immune enhancing diet (87.5% vs. 33.3%, p = 0.004). Plasma concentrations of IL-1β were higher in non-oophorectomized female rats fed with control diet compared to immune enhancing diet. Non-orchidectomized males and non-oophorectomized females exhibited similar increases in IL-10 after immune enhancing diet. Our results demonstrated that immunonutrition was more beneficial for male than female cirrhotic rats following sepsis. Though orchidectomy was not found to be more advantageous for the normal male rats in sepsis, immunonutrition seemed to be as important as sex hormone for female rats in sepsis. Full article

The apical cytoplasm of airway epithelium (AE) contains abundant labile zinc (Zn) ions that are involved in the protection of AE from oxidants and inhaled noxious substances. A major question is how dietary Zn traffics to this compartment. In rat airways, in vivo selenite autometallographic (Se-AMG)-electron microscopy revealed labile Zn-selenium nanocrystals in structures resembling secretory vesicles in the apical cytoplasm. This observation was consistent with the starry-sky Zinquin fluorescence staining of labile Zn ions confined to the same region. The vesicular Zn transporter ZnT4 was likewise prominent in both the apical and basal parts of the epithelium both in rodent and human AE, although the apical pools were more obvious. Expression of ZnT4 mRNA was unaffected by changes in the extracellular Zn concentration. However, levels increased 3-fold during growth of cells in air liquid interface cultures and decreased sharply in the presence of retinoic acid. When comparing nasal versus bronchial human AE cells, there were significant positive correlations between levels of ZnT4 from the same subject, suggesting that nasal brushings may allow monitoring of airway Zn transporter expression. Finally, there were marked losses of both basally-located ZnT4 protein and labile Zn in the bronchial epithelium of mice with allergic airway inflammation. This study is the first to describe co-localization of zinc vesicles with the specific zinc transporter ZnT4 in airway epithelium and loss of ZnT4 protein in inflamed airways. Direct evidence that ZnT4 regulates Zn levels in the epithelium still needs to be provided. We speculate that ZnT4 is an important regulator of zinc ion accumulation in secretory apical vesicles and that the loss of labile Zn and ZnT4 in airway inflammation contributes to AE vulnerability in diseases such as asthma. Full article

It has been shown that dietary materials are involved in immune regulation in the intestine. Lipids mediate immune regulation through a complex metabolic network that produces many kinds of lipid mediators. Sphingosine-1-phosphate (S1P) is a lipid mediator that controls cell trafficking and activation. In this review, we focus on the immunological functions of S1P in the regulation of intestinal immune responses such as immunoglobulin A production and unique T cell trafficking, and its role in the development of intestinal immune diseases such as food allergies and intestinal inflammation, and also discuss the relationship between dietary materials and S1P metabolism. Full article

A role for vitamin D in the regulation of immune function was first proposed after the identification of Vitamin D Receptors in lymphocytes. It has since been recognized that the active form of vitamin D, 1α,25(OH)2D3, has direct affects on naïve and activated helper T cells, regulatory T cells, activated B cells and dendritic cells. There is a growing body of literature linking vitamin D (serum 25(OH)D, oral intake and surrogate indicators such as latitude) to various immune-related conditions, including allergy, although the nature of this relationship is still unclear. This review explores the findings of epidemiological, clinical and laboratory research, and the potential role of vitamin D in promoting the inappropriate immune responses which underpin the rise in a broad range of immune diseases. Full article

The short chain fatty acids (SCFAs) acetate (C₂), propionate (C₃) and butyrate (C₄) are the main metabolic products of anaerobic bacteria fermentation in the intestine. In addition to their important role as fuel for intestinal epithelial cells, SCFAs modulate different processes in the gastrointestinal (GI) tract such as electrolyte and water absorption. These fatty acids have been recognized as potential mediators involved in the effects of gut microbiota on intestinal immune function. SCFAs act on leukocytes and endothelial cells through at least two mechanisms: activation of GPCRs (GPR41 and GPR43) and inhibiton of histone deacetylase (HDAC). SCFAs regulate several leukocyte functions including production of cytokines (TNF-α, IL-2, IL-6 and IL-10), eicosanoids and chemokines (e.g., MCP-1 and CINC-2). The ability of leukocytes to migrate to the foci of inflammation and to destroy microbial pathogens also seems to be affected by the SCFAs. In this review, the latest research that describes how SCFAs regulate the inflammatory process is presented. The effects of these fatty acids on isolated cells (leukocytes, endothelial and intestinal epithelial cells) and, particularly, on the recruitment and activation of leukocytes are discussed. Therapeutic application of these fatty acids for the treatment of inflammatory pathologies is also highlighted. Full article