A leukotriene-dependent spleen-liver axis drives TNF production in systemic inflammation.

Production of the proinflammatory cytokine tumor necrosis factor (TNF) must be precisely regulated for effective host immunity without the induction of collateral tissue damage. Here, we showed that TNF production was driven by a spleen-liver axis in a rat model of systemic inflammation induced by bacterial lipopolysaccharide (LPS). Analysis of cytokine expression and secretion in combination with splenectomy and hepatectomy revealed that the spleen generated not only TNF but also factors that enhanced TNF production by the liver, the latter of which accounted for nearly half of the TNF secreted into the circulation.

Diet-induced obesity attenuates the hypothermic response to lipopolysaccharide independently of TNF-α production.

Life-threatening infections (sepsis) are usually associated with co-morbidities, among which obesity deserves attention. Here, we evaluated whether and how obesity affects the switch from fever to hypothermia that occurs in the most severe cases of sepsis, which is thought to provide physiological support for a change in host defense strategy from resistance to tolerance. Obesity was induced by keeping rats on a high-fat diet for 32-34 weeks.

Site-Specific Reprogramming of Macrophage Responsiveness to Bacterial Lipopolysaccharide in Obesity.

The mechanisms by which obesity may alter immune responses to pathogens are poorly understood. The present study assessed whether the intrinsic responsiveness of resident macrophages to bacterial lipopolysaccharide (LPS) is reprogrammed in high-fat diet (HFD)-induced obesity. Macrophages from adipose tissue, lung alveoli, and the peritoneal cavity were extracted from obese rats on a HFD or from their lean counterparts, and subsequently studied in culture under identical conditions.

Aedes aegypti saliva impairs M1-associated proinflammatory phenotype without promoting or affecting M2 polarization of murine macrophages.

Background: During the feeding process, the mouthparts of hematophagous mosquitoes break the skin barrier and probe the host tissue to find the blood. The saliva inoculated in this microenvironment modulates host hemostasis, inflammation and adaptive immune responses. However, the mechanisms involved in these biological activities remain poorly understood and few studies explored the potential roles of mosquito saliva on the individual cellular components of the immune system.

Elucidating the role of leptin in systemic inflammation: a study targeting physiological leptin levels in rats and their macrophages.

To elucidate the role of leptin in acute systemic inflammation, we investigated how its infusion at low, physiologically relevant doses affects the responses to bacterial lipopolysaccharide (LPS) in rats subjected to 24 h of food deprivation. Leptin was infused subcutaneously (0-20 μg·kg·h) or intracerebroventricularly (0-1 μg·kg·h). Using hypothermia and hypotension as biomarkers of systemic inflammation, we identified the phase extending from 90 to 240 min post-LPS as the most susceptible to modulation by leptin.

Respiratory gas exchange as a new aid to monitor acidosis in endotoxemic rats: relationship to metabolic fuel substrates and thermometabolic responses.

This study introduces the respiratory exchange ratio (RER; the ratio of whole-body CO production to O consumption) as an aid to monitor metabolic acidosis during the early phase of endotoxic shock in unanesthetized, freely moving rats. Two serotypes of lipopolysaccharide (lipopolysaccharide [LPS] O55:B5 and O127:B8) were tested at shock-inducing doses (0.5-2 mg/kg).

Spontaneous hypothermia in human sepsis is a transient, self-limiting, and nonterminal response.

Hypothermia in sepsis is generally perceived as something dysregulated and progressive although there has been no assessment on the natural course of this phenomenon in humans. This was the first study on the dynamics of hypothermia in septic patients not subjected to active rewarming, and the results were surprising. A sample of 50 subjects presenting with spontaneous hypothermia during sepsis was drawn from the 2005-2012 database of an academic hospital.

Hypometabolism and hypothermia in the rat model of endotoxic shock: independence of circulatory hypoxia.

We tested the hypothesis that development of hypothermia instead of fever in endotoxic shock is consequential to hypoxia. Endotoxic shock was induced by bacterial lipopolysaccharide (LPS, 500 μg kg(-1) i.v.