Dual role of lipoxin A4 in pneumosepsis pathogenesis.

Lipoxin A4 (LXA4) is an endogenous lipid mediator with potent anti-inflammatory actions but its role in infectious processes is not well understood. We investigated the involvement of LXA4 and its receptor FPR2/ALX in the septic inflammatory dysregulation. Pneumosepsis was induced in mice by inoculation of Klebsiella pneumoniae. LXA4 levels and FPR2/ALX expression in the infectious focus as well as the effects of treatment with receptor agonists (LXA4 and BML-111) and antagonists (BOC-2 and WRW(4)) in early (1h) and late (24h) sepsis were studied. Sepsis induced an early increase in LXA4, FPR2/ALX lung expression, local and systemic infection and inflammation, and mortality. Treatment with BOC-2 in early sepsis increased leukocyte migration to the focus, and reduced bacterial load and dissemination. Inhibition of 5- and 15-lipoxygenase in early sepsis also increased leukocyte migration. Early treatment with WRW(4) and BOC-2 improved survival. Treatment with authentic LXA4 or BML-111 in early sepsis decreased cell migration and worsened the infection. In late sepsis, treatment with BOC-2 had no effect, but LXA4 improved the survival rate by reducing the excessive inflammatory response, this effect being abolished by pretreatment with BOC-2. Thus, the anti-inflammatory and pro-resolution mediator LXA4 and its receptor FPR2/ALX levels were increased in the early phase of sepsis, contributing to the septic inflammatory dysregulation. In addition, LXA4 has a dual role in sepsis and that its beneficial or harmful effects are critically dependent on the time. Therefore, a proper interference with LXA4 system may be a new therapeutic avenue to treat sepsis.

Resting energy expenditure, body composition, and dietary intake: a longitudinal study before and after liver transplantation.

BACKGROUND: The loss of hepatic innervations after liver transplantation (LTx) might affect the energy metabolism of the patients. The aim of this study was to assess the resting energy expenditure (REE), body composition, and dietary intake before and during the first year after the LTx. METHODS: The REE was measured by indirect calorimetry. Nutritional status was assessed by anthropometric assessment, bioimpedance, handgrip strength, and dietary intake (before and 30, 90, 180, 270, and 370 days after LTx). Social, clinical, and nutritional variables were assessed as being potentially associated with REE or hypermetabolism and hypometabolism after LTx. RESULTS: Seventeen patients were included. REE was elevated at 30 days and reduced at the end of the study (P<0.05). Hypermetabolism/hypometabolism were low but present at the end of the study (11.8% of each). Increases in body weight and fat mass were observed (P<0.05). Handgrip strength and phase angle improved after LTx (P<0.05). Energy balance was positive at all times after LTx, and an increase in fat intake occurred (P<0.05). After multivariate analyses (P<0.05), the REE before transplantation and triceps skinfold thickness were positively associated and the cumulative dose of prednisone was negatively associated with REE after LTx. The presence of hypermetabolism was significantly associated with the presence of hypermetabolism before LTx and the cumulative dose of prednisone. Percentage of fat intake and fat mass before LTx was associated with hypometabolism. CONCLUSION: Some potential modifiable factors are related to resting energy metabolism in patients undergoing LTx. Adequate and individualized nutritional guidance should be started before LTx.