leptin and Multiple-Organ-Failure

Heart-type fatty acid-binding protein (H-FABP) is widely distributed and has been used to diagnose certain diseases. However, its alteration during infection-evoked organ dysfunction, and the potential association between leptin and it in injury or infection has not been investigated. In the current study, serum H-FABP, leptin, C-reactive protein and interleukin-1beta in the patients with pulmonary infection-induced multiple organ dysfunction were detected. Moreover, a mouse model of sepsis was established, and serum alanine transaminase, uric acid, tissue H-FABP, myeloperoxidase, superoxide dismutase activity and histological alterations in lung and intestine were investigated. Serum H-FABP and leptin increased simultaneously and significantly in the patients, and leptin alleviated pulmonary and intestinal injuries by restraining tissue H-FABP secretions in the mouse model of sepsis. Other investigated variables showed different but independent alterations. In conclusion, H-FABP represents a useful diagnostic marker for organ dysfunction, and its association with leptin will be a novel target for emergency aid.

Topics: Adult; Alanine Transaminase; Animals; Biomarkers; C-Reactive Protein; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Female; Humans; Interleukin-1beta; Leptin; Male; Mice; Middle Aged; Multiple Organ Failure; Peroxidase; Rabbits; Radioimmunoassay; Reproducibility of Results; Sepsis; Superoxide Dismutase; Uric Acid

Humoral mediators are potentially involved in the pathogenesis of postoperative complications following surgery. The aim of the present study is to evaluate the postoperative responses of circulating cytokines, chemokines, and stress hormones following liver resection, and their effects on postoperative infectious complications and organ dysfunction.. Perioperative plasma concentrations of interleukin (IL)-6, IL-10, IL-4, IL-8, macrophage chemoattractant protein (MCP)-1, cortisol, macrophage migration inhibitory factor (MIF), and leptin were measured by immunoassays in 128 consecutive patients undergoing liver resection.. Forty-three patients had postoperative infection and 11 had infection-related organ dysfunction. Plasma levels of all mediators except for IL-4 increased postoperatively. Postoperative levels of IL-6, IL-10, IL-8, MCP-1, cortisol, and leptin were significantly higher in patients with organ dysfunction than in those without organ dysfunction (P < 0.05). However, postoperative MIF levels were not affected by postoperative infection or organ dysfunction. Plasma levels of IL-6, IL-10, IL-8, and MCP-1 were positively correlated with operation time (P < 0.0001) or blood loss (P < 0.0001), and higher in patients with jaundiced liver (P < 0.05). In univariate logistic regression analyses, elevated IL-6, IL-10, IL-8, and MCP-1, advanced age, large volume of blood loss, long operation time, long hepatic ischemia time, and major liver resection were significantly correlated with postoperative infection (P < 0.05). In multivariate analyses, IL-6 and IL-10 were significant predisposing factors for postoperative infection (P < 0.05), and blood loss and IL-6 for organ dysfunction (P < 0.01).. These results suggest that IL-6, IL-10, IL-8, MCP-1, cortisol, and leptin are released after liver resection in response to surgical stress and correlated with postoperative infection and organ dysfunction, and that of these circulating mediators, IL-6 and IL-10, have a close relationship to the complications.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chemokine CCL2; Cytokines; Female; Humans; Hydrocortisone; Infections; Interleukin-10; Interleukin-4; Interleukin-6; Interleukin-8; Leptin; Linear Models; Liver Diseases; Macrophage Migration-Inhibitory Factors; Male; Middle Aged; Multiple Organ Failure; Postoperative Complications; Stress, Physiological; Treatment Outcome

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

Hypercatabolism and immune dysfunction are closely associated with the development of systemic inflammatory response--multiple organ dysfunction (SIRS/MODS) in critical illness. It remains unclear however, whether leptin, an adipocyte-derived hormone whose levels are influenced by several cytokines and which regulates immune function, food-intake and energy expenditure is independently related to the development of and/or severity and mortality from SIRS/MODS.. To assess the role of leptin in SIRS/MODS we performed a matched case control and a longitudinal study (14 days) in 35 critically ill patients with SIRS/MODS and 35 matched controls.. Baseline leptin levels were positively associated with body mass index (BMI) and TNF-alpha (P < 0.01) in patients and with IGF-1 and IL-6 levels (P < 0.05) in controls. Furthermore, leptin levels exhibited a progressive increase from the first to the last day of the study and although baseline levels were not different, peak leptin levels as well as leptin levels on the last day of the study were significantly higher in cases than in controls (P < 0.05). TNF-alpha levels, IL-6 and cortisol levels were also higher, whereas IGF-1 levels were lower in cases (P < 0.05). To assess whether leptin levels are independently associated with SIRS/MODS we performed multivariate logistic regression analysis which revealed that leptin up-regulation in cases is mediated by elevated TNF-alpha and cortisol levels. Finally, there was no independent association between leptin and survival in this group of critically ill patients.. We conclude that cytokines and cortisol upregulate leptin levels, which may contribute to the development of the hypercatabolism, wasting and immune dysfunction but leptin levels are not independently associated with severity or mortality of patients with systemic inflammatory response-multiple organ dysfunction.

Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Case-Control Studies; Female; Humans; Hydrocortisone; Insulin-Like Growth Factor I; Interleukin-6; Leptin; Logistic Models; Longitudinal Studies; Male; Middle Aged; Multiple Organ Failure; Survival Rate; Tumor Necrosis Factor-alpha