Leptin improves pulmonary bacterial clearance and survival inob/obmice during pneumococcal pneumonia

Abstract

SummaryThe adipocyte-derived hormone leptin is an important regulator of appetite and energy expenditure and is now appreciated for its ability to control innate and adaptive immune responses. We have reported previously that the leptindeficient ob/ob mouse exhibited increased susceptibility to the Gram-negative bacterium Klebsiella pneumoniae. In this report we assessed the impact of chronic leptin deficiency, using ob/ob mice, on pneumococcal pneumonia and examined whether restoring circulating leptin to physiological levels in vivo could improve host defences against this pathogen. We observed that ob/ob mice, compared with wild-type (WT) animals, exhibited enhanced lethality and reduced pulmonary bacterial clearance following Streptococcus pneumoniae challenge. These impairments in host defence in ob/ob mice were associated with elevated levels of lung tumour necrosis factor (TNF)-a, macrophage inflammatory peptide (MIP)-2 [correction added after online publication 28 September 2007: definition of MIP corrected], prostaglandin E2 (PGE2), lung neutrophil polymorphonuclear leukocyte (PMN) counts, defective alveolar macrophage (AM) phagocytosis and PMN killing of S. pneumoniae in vitro.Exogenous leptin administration to ob/ob mice in vivo improved survival and greatly improved pulmonary bacterial clearance, reduced bacteraemia, reconstituted AM phagocytosis and PMN H2O2 production and killing of S. pneumoniae in vitro. Our results demonstrate, for the first time, that leptin improves pulmonary bacterial clearance and survival in ob/ob mice during pneumococcal pneumonia. Further investigations are warranted to determine whether there is a potential therapeutic role for this adipokine in immunocompromised patients.

Serum Leptin is Decreased Thirty Days after Surgery

“…In humans, leptin has also been shown to be a predictor of lung function and lung volume [27]. In contrast to our study serum leptin concentrations are often reported to be increased in inflammatory and infectious conditions [28,29].…”

Obesity is associated with improved survival in community-acquired pneumonia

“…The role of leptin in the response to sepsis and pulmonary infections remains a subject of debate. Mouse models of leptin deficiency (ob/ob mice) have exhibited reduced bacterial clearance and increased mortality, shown to be related to impaired alveolar macrophage phagocytosis, reduced lung neutrophil counts and levels of pro-inflammatory cytokines [30,31]. Exogenous administration of leptin improved survival and pulmonary bacterial clearance and reduced bacteraemia in ob/ob mice [31].…”

Leptin and Inflammation

“…A protective role of leptin in the clearance from pathogens is observed in leptin-deficient ob/ ob mice, which develop severe disease and die of infection with Klebsiella more rapidly than wild-type mice [102][103]. The ob/ob mice are also highly susceptible to LPS-induced lethality, which can be reversed by the administration of leptin [104][105].…”