Sex differences in the influence of obesity on a murine model of allergic lung inflammation.

BACKGROUND: Despite the overwhelming evidence showing the influence of sex or obesity in the development of respiratory diseases in humans and animals, the mechanisms by which these combined two factors influence allergic asthma are not well understood. OBJECTIVE: We have investigated the interaction between sex and weight gain in an experimental model of lung allergic inflammation induced by chicken egg ovalbumin (OVA) in mice. METHODS: Animals were fed a high-fat diet for 8 weeks and then sensitized and challenged with OVA. RESULTS: Our results demonstrate that in comparison with males, high-fat diet (HFD) allergic female mice exhibit a reduction in the number of leucocytes in the lung lumen when challenged with OVA and, in contrast, an accumulation of these cells in the lung tissue. In addition, we also observed that allergic HFD female mice presented a robust lung remodelling in comparison with HFD males, evidenced by higher deposition of collagen in the airways and TGF-ß in lung fluid. Measuring epithelial adhesion molecule expression, we observed that female mice presented a significantly lower expression of CD103 than males in BAL cells, regardless of the diet. Similarly, HFD female mice express lower levels of EpCAM in lung tissue in comparison with males and lean females. Levels of A20/TNFAIP3 expression in lung tissue demonstrated that HFD female mice express lower levels of these regulatory factors than all the other groups. However, this reduction was not accompanied by an increase in activated NF-κB. CONCLUSIONS: Our results present evidence that the interaction between sex and weight gain alters the progression of allergic asthma in mice with females developing airway remodelling at a much earlier stage than males. CLINICAL RELEVANCE: These data may contribute to a better understanding of the clinical differences in the development and severity of allergic asthma observed between men and women of reproductive age.

Alternative and/or integrative therapies for pneumonia under development.

PURPOSE OF REVIEW: Increasing antimicrobial resistance among common respiratory bacteria has created challenges in selecting appropriate therapy for pneumonia. Fortunately, the analysis of genome sequences has allowed us to find novel, nontraditional targets that are involved in disease pathogenesis or in adaptation and growth in infection sites. The advantage of the nonclassical targets is that targeting these sites could ablate infection without inducing resistance. Interfering with bacterial adhesion, inhibiting, neutralizing and clearing endotoxin, and administering cytokines as immunoadjuvants are the most promising alternative or integrative treatments for pneumonia that are under development. RECENT FINDINGS: Interference with bacterial adhesion is possible using inhibitors of sortase or inactivators of the srtA gene against gram-positive bacteria, inhibitors of the periplasmic chaperone or those of usher function against gram-negative bacteria, novel polysaccharides that are present on echinoderm surfaces, antiadhesin vaccines, or the passive administration of antiadhesin antibodies. Inhibition, neutralization, and clearance of endotoxin possibly interferes in the lipid A biosynthetic pathway or using lipid A analogues with reduced or lack of ability to activate the major endotoxin receptors or proteins such as recombinant Limulus antilipopolysaccharide factor, bactericidal/permeability increasing protein, or lipopolysaccharide binding protein. Tumor necrosis factor 70-80, an adenoviral vector that encodes murine tumor necrosis factor alpha, and recombinant interferon gamma seem to be the most promising cytokines for use as immunoadjuvants for the treatment of pneumonia. SUMMARY: Ideally, potential treatment of life-threatening bacterial pneumonia will combine immunoadjuvant and conventional antibiotic therapy. Compounds capable of stimulating early host defense and microbial clearance, but not the later phases of inflammatory tissue injury associated with sepsis, may be advantageous.