leptin and Pneumonia

Respiratory viruses are associated with significant global morbidity and mortality, as well as socioeconomic factors. Certain conditions and patient groups are more susceptible to develop severe viral respiratory tract infections (RTIs).. To summarise the data on deregulated immune pathways that have been associated with increased susceptibility to severe viral RTIs in certain populations. We also describe the commonalities of the defective immune pathways across these susceptible populations that may represent possible targets for future therapeutic or preventative approaches.. We conducted free searches in Medline, Scopus, and Google Scholar for studies focusing on potential mechanisms of immune dysfunction that may be associated with severe viral RTIs in susceptible populations with conditions including pregnancy, obesity, diabetes mellitus, hypertension, cardiovascular disease, asthma, chronic obstructive pulmonary disease (COPD), chronic kidney disease, and extremes of age. We considered preclinical/animal data, original human studies, and reviews.. Innate and adaptive immune responses become quantitatively and qualitatively compromised in aging, obesity, and diabetes mellitus, with the most pronounced changes affecting T cells. Moreover, immune dysregulation by the so-called inflamm-aging results in chronic low-grade inflammation in such conditions. Increased leptin levels affect the immune system particularly in obesity, while leptin dysregulation plays a role in asthma and COPD pathogenesis. Deficient production of interferon (IFN) type I and III in response to rhinovirus contributes to asthma exacerbations. Similar attenuation of IFN production in response to influenza and rhinovirus has been documented in pregnancy. Dampened type I IFN responses have also been found in diet-induced obese mice and in obese individuals.. Immunosenescence and chronic low-grade inflammation accompanying aging and a variety of chronic conditions, such as diabetes, obesity, asthma, COPD, chronic renal disease, and hypertension, contribute to the poor outcomes observed following viral respiratory infections. Commonly affected pathways may represent potential future therapeutic targets.

Topics: Animals; Asthma; Disease Susceptibility; Enterovirus Infections; Humans; Hypertension; Immunity; Inflammation; Interferons; Leptin; Mice; Obesity; Pneumonia; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Rhinovirus

Leptin is an adipocyte-derived hormone, recognized as a critical mediator of the balance between food intake and energy expenditure by signalling through its functional receptor (Ob-Rb) in the hypothalamus. Structurally, leptin belongs to the long-chain helical cytokine family, and is now known to have pleiotropic functions in both innate and adaptive immunity. The presence of the functional leptin receptor in the lung together with evidence of increased airspace leptin levels arising during pulmonary inflammation, suggests an important role for leptin in lung development, respiratory immune responses and eventually pathogenesis of inflammatory respiratory diseases. The purpose of this article is to review our current understanding of leptin and its functional role on the different resident cell types of the lung in health as well as in the context of three major respiratory conditions being chronic obstructive pulmonary disease (COPD), asthma, and pneumonia.

Topics: Adaptive Immunity; Animals; Asthma; Humans; Immunity, Innate; Inflammation; Leptin; Lung; Pneumonia; Pulmonary Disease, Chronic Obstructive

The number of overweight and obese individuals has dramatically increased in the US and other developed nations during the past 30 years. While type II diabetes and cardiovascular disease are well recognized co-morbid conditions associated with obesity, recent reports have demonstrated a greater severity of illness in obese patients due to influenza during the 2009 H1N1 pandemic. Consistent with these reports, diet-induced obesity has been shown to impair anti-viral host defense in murine models of influenza infection. However, the impact of obesity on the risk of community-acquired and nosocomial pneumonia in human patients is not clear. Relatively few studies have evaluated the influence of diet-induced obesity in murine models of bacterial infections of the respiratory tract. Obese leptin deficient humans and leptin and leptin-receptor deficient mice exhibit greater susceptibility to respiratory infections suggesting a requirement for leptin in the pulmonary innate and adaptive immune response to infection. In contrast to these studies, we have observed that obese leptin receptor signaling mutant mice are resistant to pneumococcal pneumonia highlighting the complex interaction between leptin receptor signaling and immune function. Given the increased prevalence of obesity and poor responsiveness of obese individuals to vaccination against influenza, the development of novel immunization strategies for this population is warranted. Additional clinical and animal studies are needed to clarify the relationship between increased adiposity and susceptibility to community-acquired and nosocomial pneumonia.

Topics: Adiposity; Animals; Bacterial Infections; Disease Models, Animal; Humans; Influenza, Human; Leptin; Mice; Obesity; Pneumonia; Receptors, Leptin; Respiratory Tract Infections; Severity of Illness Index; United States

Alveolar macrophages (AMs) are critical mediators of pulmonary inflammation. Given the unique lung tissue environment, whether there exist AM-specific mechanisms that control inflammation is not known. Here, we found that among various tissue-resident macrophage populations, AMs specifically expressed

Topics: Humans; Inflammation; Leptin; Lung; Macrophages, Alveolar; Pneumonia; Receptors, Leptin

Topics: Animals; Cell Line, Tumor; Cyclooxygenase 2; Group IV Phospholipases A2; Humans; Leptin; Lung; Male; Mice; Mice, Inbred ICR; NADPH Oxidases; Oxidative Stress; Pneumonia; Reactive Oxygen Species; Receptors, Leptin

Accumulating evidence suggests that maternal obesity increases the risk of their offspring developing noncommunicable diseases later in life, but the potential mechanisms, especially those resulting in abnormal respiratory conditions, are not thoroughly understood. Here, we used maternal high-fat diet (HFD) feeding during premating, pregnancy, and lactation to investigate the effect of maternal HFD on offspring lung development. Offspring birth weight and body weight and composition were measured. Serum leptin levels were measured by ELISA. Hematoxylin-eosin (H&E) and Masson's staining were used in paraffin-embedded lung sections. Levels of transfer growth factor-β (TGF-β) and α-smooth muscle actin (α-SMA) were examined by immunohistochemistry and western blot, respectively. Maternal HFD feeding during pregnancy and lactation lead to higher birth weight, final body weight, fat accumulation and hyperleptinemia in offspring. Maternal HFD feeding aggravated lung inflammatory response in the offspring, resulting in inflammatory cell infiltration and collagen deposition potentially via the enhanced expression of TGF-β and α-SMA in the offspring.

Topics: Actins; Animals; Birth Weight; Body Composition; Body Weight; Diet, High-Fat; Enzyme-Linked Immunosorbent Assay; Female; Lactation; Leptin; Lung; Male; Pneumonia; Pregnancy; Prenatal Exposure Delayed Effects; Rats, Sprague-Dawley; Transforming Growth Factor beta

Topics: Animals; Asthma; Humans; Leptin; Pneumonia; Pulmonary Disease, Chronic Obstructive

Obesity is associated with a high circulating leptin level and severe 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) infection. The mechanism for severe lung injury in obese patients and the specific treatment strategy remain elusive.. We studied the pathogenesis of A(H1N1)pdm09 infection in a mouse model of diet-induced obesity.. Obese mice had significantly higher initial pulmonary viral titer and mortality after challenge with A(H1N1)pdm09, compared with age-matched lean mice. Compared with lean mice, obese mice had heightened proinflammatory cytokine and chemokine levels and more severe pulmonary inflammatory damage. Furthermore, obese mice had a higher preexisting serum leptin level but a lower preexisting adiponectin level. Recombinant mouse leptin increased the interleukin 6 (IL-6) messenger RNA expression in mouse single-lung-cell preparations, mouse macrophages, and mouse lung epithelial cell lines infected with A(H1N1)pdm09. Administration of anti-leptin antibody improved the survival of infected obese mice, with associated reductions in pulmonary levels of the proinflammatory cytokines IL-6 and interleukin 1β but not the pulmonary viral titer.. Our findings suggest that preexisting high levels of circulating leptin contribute to the development of severe lung injury by A(H1N1)pdm09 in mice with diet-induced obesity. The therapeutic strategy of leptin neutralization for the reduction of proinflammatory responses and pulmonary damage in obese patients warrants further investigations.

Topics: Animals; Antibodies; Diet, High-Fat; Disease Models, Animal; Epithelium; Female; Influenza A Virus, H1N1 Subtype; Interleukin-1beta; Interleukin-6; Kaplan-Meier Estimate; Leptin; Lung; Macrophages; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Orthomyxoviridae Infections; Pandemics; Pneumonia; Recombinant Proteins; RNA, Messenger; Viral Load

Leptin, a pleiotropic type I cytokine, was recently demonstrated to be expressed by resident lung cells in chronic obstructive pulmonary disease patients and asymptomatic smokers. To elucidate the functional role of leptin in the onset of chronic obstructive pulmonary disease, we tested leptin-deficient ob/ob mice (C57BL/6), leptin receptor-deficient db/db mice (C57BKS), and littermates in a model of cigarette smoke (CS)-induced pulmonary inflammation. Wild-type (WT) C57BL/6 mice were exposed for 4 or 24 wk to control air or CS. Pulmonary leptin expression was analyzed by immunohistochemistry and real-time PCR. Pulmonary inflammation upon 4 wk CS exposure was evaluated in bronchoalveolar lavage fluid (BALF) and lung tissue of WT, ob/ob, and db/db mice. Immunohistochemical analysis revealed leptin expression in bronchial epithelial cells, pneumocytes, alveolar macrophages, and bronchial/vascular smooth muscle cells. The 4 and 24 wk CS exposure increased leptin expression in bronchial epithelial cells and pneumocytes versus air-exposed WT mice (p<0.05). The 4 wk CS exposure resulted in increased accumulation of neutrophils, dendritic cells, macrophages, and lymphocytes in BALF and lung tissue of WT, ob/ob, and db/db mice. CS-exposed ob/ob and db/db mice showed in general higher numbers of neutrophils and lower numbers of CD4+, CD8+, and dendritic cells versus CS-exposed WT mice. Consistently, CXCL1 levels were enhanced in BALF of CS-exposed ob/ob and db/db mice versus WT mice (p<0.05). Exogenous leptin administration completely restored the skewed inflammatory profile in ob/ob mice. These data reveal an important role of leptin in modulating innate and adaptive immunity after CS inhalation in mice.

Topics: Adaptive Immunity; Animals; Bronchoalveolar Lavage Fluid; Chemotaxis, Leukocyte; Enzyme-Linked Immunosorbent Assay; Immunity, Innate; Immunohistochemistry; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Pneumonia; Pulmonary Disease, Chronic Obstructive; Receptors, Leptin; Respiratory Mucosa; Reverse Transcriptase Polymerase Chain Reaction; Tobacco Smoke Pollution

To determine whether leptin in patients with CAP acts as a nutritional or as an inflammatory marker and whether leptin plays any role regarding survival, we included 222 patients diagnosed of CAP, 142 men and 80 women, median age 74 years. We did not find significant differences in serum leptin levels between CAP patients and healthy controls, even after adjusting by BMI. Serum leptin levels were directly related with BMI, body fat and muscle mass and inversely related with inflammatory markers, including pro- and anti-inflammatory cytokines. Patients with positive blood cultures showed lower serum leptin and raised inflammatory markers. Although patients who died showed lower values of serum leptin, multivariate analysis showed that the prognostic value of low serum leptin levels depends on impaired nutritional status. In conclusion, we suggest that in CAP patients, leptin does not act as an inflammatory reactant but as a nutritional marker.

Topics: Acute-Phase Reaction; Adult; Aged; Aged, 80 and over; Community-Acquired Infections; Female; Humans; Leptin; Male; Middle Aged; Nutritional Status; Pneumonia

Leptin is a satiety hormone that also has proinflammatory effects, including augmentation of ozone-induced pulmonary inflammation. The purpose of this study was to determine whether reductions in endogenous levels of leptin can attenuate pulmonary responses to ozone. To reduce serum leptin, we fasted mice overnight before ozone exposure. Fasting caused a marked reduction in serum leptin to approximately one-sixth the levels observed in fed mice, and continuous infusion of leptin via Alzet micro-osmotic pumps restored serum leptin to, but not above, fed levels. Ozone exposure (2 ppm for 3 h) caused a significant, approximately 40% increase in pulmonary resistance (P < 0.01) and increased airway responsiveness in fasted but not in fed mice. The increased effect of ozone on pulmonary mechanics and airway responsiveness in fasted mice was not observed when leptin was restored via continuous infusion. Ozone exposure caused pulmonary inflammation, as evident by increases in bronchoalveolar lavage cells, protein, and soluble tumor necrosis factor receptors. There was no effect of fasting status on ozone-induced changes in the bronchoalveolar lavage inflammatory profile, and leptin treatment did not alter these responses. Our results indicate that fasting augments ozone-induced changes in pulmonary mechanics and airway responsiveness in mice. These effects of fasting are the result of declines in serum leptin. The mechanistic basis for this protective effect of leptin in fasted mice remains to be determined but is not related to effects on ozone-induced inflammation.

Topics: Airway Resistance; Animals; Body Mass Index; Bronchial Hyperreactivity; Corticosterone; Fasting; Leptin; Male; Mice; Mice, Inbred C57BL; Oxidants, Photochemical; Ozone; Pneumonia; Respiratory Mechanics

To determine serum levels of leptin and some related cytokines in severely ill patients, including severe pulmonary infection-induced multiple organ dysfunction syndrome (MODS), acute myocardial infarction (AMI) and arrhythmia (AR), and to explore the possible role of leptin in the pathogenesis and diagnosis of MODS.. Radioimmunoassay was used to determine leptin, fatty acid binding protein (FABP), transferrin (Ferr) and interleukin-1beta (IL-1beta), and enzyme-linked immuno adsorbent assay (ELISA) was used to assess C reactive protein (CRP).. Compared with normal individuals, leptin levels in MODS, AMI and AR patients increased significantly (all P<0.01). CRP and IL-1beta levels also increased significantly in MODS, AMI and AR patients, but the changes were more marked (all P<0.05) in MODS patients than in the patients of other two diseases (both P<0.05). Though FABP and Ferr levels of patients in all the three groups of patients showed a trend toward increase, especially in MODS patients, there was no significant difference between them and normal individuals.. Serum leptin level increases significantly in pulmonary infection-induced MODS patients with a simultaneous increase of CRP and IL-1beta levels, and the result suggests that leptin plays a possible role in the pathogenesis and prognosis of MODS.

Topics: C-Reactive Protein; Case-Control Studies; Fatty Acid-Binding Proteins; Humans; Interleukin-1beta; Leptin; Multiple Organ Failure; Pneumonia