leptin and Peritonitis

Adipose tissue is a major site of chronic inflammation associated with peritoneal dialysis (PD) frequently complicating peritonitis. Adiposity-associated inflammation plays a significant contributory role in the development of chronic inflammation in patients undergoing maintenance PD. However, the molecular and cellular mechanisms of this link remain uncertain. Adipose tissue synthesizes different adipokines and cytokines that orchestrate and regulate inflammation, insulin action, and glucose metabolism locally and systemically. In return, inflammation retards adipocyte differentiation and further exacerbates adipose dysfunction and inflammation. An understanding of the inflammatory roles played by adipose tissue during PD and the healing mechanism of injured mesothelium will help to devise new therapeutic approach to slow the progression of peritoneal damage during peritoneal dialysis. This article reviews the roles of peritoneal adipose tissue in chronic peritoneal inflammation under PD and in serosal repair during PD.

Topics: Adipocytes; Adipokines; Adipose Tissue; Antigens, CD; Endothelial Cells; Humans; Inflammation; Leptin; Peritoneal Dialysis; Peritonitis; Polymerase Chain Reaction; Regeneration; RNA, Messenger; Stem Cells

Leptin (LEP) and its receptor (LEPR) participate in the immunological response during infection. LEP serum levels rise during sepsis. In patients with peritonitis, an insufficient elevation in serum LEP is associated with an increased risk of death. As gene variants of LEP and LEPR have been associated with diverse pathologic conditions, we explored the association of genetic polymorphisms of LEP or LEPR with death in patients with secondary peritonitis.. A case control study was undertaken. LEP Gene -2548G > A and the LEPR Gene 223A > G polymorphism were determined in 74 patients. The odds ratio of genotype and allele distribution in survival (control) versus death (case) among patients was calculated. Serum LEP, interleukin (IL)-6, tumour necrosis factor alpha, C-reactive protein (C-RP), IL-10 and IL-13 levels were analyzed in 34 patients.. There were significant differences in genotype and allele distribution between survivors and non-survivors for -2548G > A and 223A > G polymorphisms. The presence of the mutant allele A, in -2548, had an odds ratio of 4.64 (95% CI 1.22, 17.67) with significance (P = 0.017) in the risk of death. The presence of mutant allele G, in 223, had an odds ratio of 3.57 (95% CI 1.06, 12.01) with significance in the risk of death (P = 0.033). The presence of allele A in the -2548 polymorphism was associated with differences in serum LEP (P = 0.013), and IL-10 (P = 0.0001). The presence of allele G in 223 polymorphism was likewise correlated with differences in serum LEP (P < 0001), C-RP (P = 0.033), and IL-10 (P = 0.043).. The polymorphisms studied are associated with death in patients with peritonitis of non-appendicular origin. This association is stronger than many known risk-factors related to peritonitis severity, and is independent of body mass. The physiopathologic mechanism is possibly related to an insufficient increase in the elevation of serum LEP levels, and is unrelated to body mass.

Topics: Adult; Aged; Appendicitis; Biomarkers; Case-Control Studies; Female; Humans; Leptin; Male; Middle Aged; Peritonitis; Polymorphism, Genetic; Prognosis; Prospective Studies; Receptors, Leptin; Survival Analysis

We aimed to investigate the impact of C-reactive protein (CRP), interleukin (IL)-6, leptin, cortisol, and caspase-3 on the decision of terminating planned abdominal repair in secondary peritonitis.. Fifteen patients with peritonitis were enrolled into the study. Serum CRP, IL-6, leptin, cortisol, and peritoneal caspase-3 activities were measured.. APACHE II scores at 48 hours (h) and age were significantly higher in non-survivors. A significant decrease was observed in caspase-3 activities of patients in whom ≤4 laparotomies were performed when compared with those who underwent >4 laparotomies. For patients who underwent ≤4 laparotomies, there was a significant difference in caspase-3 levels between 0 and 72 h. There was no significant difference in caspase-3 levels in non-survivors; caspase-3 levels were significantly lower in the survivors at 48 and 72 h. Changes in CRP, IL-6, leptin, and cortisol levels were not statistically significant.. CRP, IL-6, leptin, cortisol, and caspase-3 are not valuable in discriminating the number of planned operations, even though there is a significant decrease in caspase-3 "within" survivors. The discriminative value of caspase-3 for closure should be evaluated in studies in which caspase-3 is monitored for a longer duration in a large number of patients.

Topics: Adult; Aged; APACHE; Ascitic Fluid; C-Reactive Protein; Caspase 3; Decision Making; Female; Humans; Hydrocortisone; Interleukin-6; Laparoscopy; Leptin; Male; Middle Aged; Peritonitis; Predictive Value of Tests; Prospective Studies; Young Adult

IL-17A is a proinflammatory cytokine critical for host defense and involved in the pathogenesis of autoimmune disorders. Obesity is associated with chronic low-grade inflammation but also with a heightened acute inflammatory response. We investigated the effect of obesity on IL-17A production using the model of ZY-induced peritonitis. Compared with lean controls, administration of ZY induced a significantly exacerbated inflammatory response in obese leptin-deficient ob/ob mice and in mice with diet-induced obesity (DIO). Levels of IL-17A in the peritoneal fluid in response to ZY were elevated significantly in ob/ob and DIO mice compared with lean animals. Reconstitution of ob/ob mice with exogenous leptin did not alter production of IL-17A significantly in response to ZY. Peritoneal cells and adipose tissue obtained from ZY-injected obese mice expressed significantly higher levels of IL-17A mRNA compared with lean mice. Approximately 2% of peritoneal Ly6G(+) neutrophils from ZY-injected obese mice expressed IL-17A protein, compared with 0.2% of cells obtained from lean mice. Neutralization of IL-17 in ob/ob mice inhibited neutrophil recruitment and production of neutrophil-attracting CXC chemokines and IL-6, without affecting macrophage infiltration or levels of IL-10 and the chemokine CCL2. In contrast, neutralization of IL-6 did not affect production of IL-17A or chemokines while reducing production of the acute-phase protein serum amyloid A significantly. These data demonstrate that neutrophil-derived IL-17A is increased in obese mice during acute inflammation and contributes to exacerbation of inflammatory responses.

Topics: Acute Disease; Animals; Ascitic Fluid; Chemokines, CXC; Dietary Fats; Female; Gene Expression Regulation; Inflammation; Interleukin-17; Interleukin-6; Intra-Abdominal Fat; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Neutrophils; Obesity; Peritonitis; T-Lymphocyte Subsets; Thinness; Zymosan

Topics: Acute Disease; Adipose Tissue; Animals; CD4-Positive T-Lymphocytes; Diet; Female; Humans; Immunity, Innate; Inflammation; Interleukin-17; Leptin; Mice; Mice, Obese; Neutrophils; Obesity; Peritonitis; Zymosan

Leptin is involved in the sepsis syndrome. A possible relationship exists between low leptin levels and peritonitis severity and a poorer prognosis.. We aimed to corroborate the relationship between low leptin serum levels and death in patients with peritonitis and to explore the associations between leptin and interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-13 (IL-13), tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP).. In 230 adult patients with surgically confirmed secondary peritonitis, the Mannheim Peritonitis Index and the serum concentrations of leptin, IL-6, IL-10, IL-13, TNF-alpha and CRP were determined. Two cohorts were established (leptin < or = 10 ng/ml and > 10 ng/ml). Death or survival was followed through 30 days. The relationship between leptin (< or = 10 ng/ml) and death was evaluated using the accumulated incidence ratio (AIR). The association of leptin (dependent variable) with IL-6, IL-10, IL-13, TNF-alpha and CRP (independent variables) was studied by regression analysis.. The general mortality rate was 7.8% and the death AIR was 3.15 (p nonsignificant). A subsample of patients with a Mannheim Peritonitis Index > or = 21 was studied, showing a significant AIR of 4.26 (p = 0.017). Regression analysis determined an association only between leptin and IL-6 (p < 0.001), IL-10 (p < 0.047) and CRP (p < 0.001).. A serum leptin below the threshold of 10 ng/ml is an adverse prognostic marker in patients with moderate to severe secondary peritonitis. The results of the regression analysis suggest that the mechanisms involved are opposing, in that leptin associated with IL-6 has a proinflammatory effect and, through IL-10 and CRP production, restrains the inflammatory response.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Female; Humans; Interleukin-10; Interleukin-13; Interleukin-6; Leptin; Male; Middle Aged; Peritonitis; Predictive Value of Tests; Prognosis; ROC Curve; Tumor Necrosis Factor-alpha

To explore the effect of acute intra-peritoneal infection on leptin expression levels in peripheral blood and vital organs, and find out the role leptin plays in acute inflammation.. A cecal ligation and perforation model of rats was established, setting groups of sham-operation, intralipid injection, injury, estradiol injection and insulin injection. A rat leptin radioimmunoassay was used to check serum leptin concentrations at 12 h after the injury, and RT-PCR was also used to detect leptin mRNA expressions in adipose tissue, lung and liver.. Compared with serum leptin level of sham-operation group after injury, that of all the other four groups showed no significant difference, while the level of intralipid group was significantly higher than that of injury group and estradiol group. Compared with leptin mRNA expression level of sham-operation group after injury, that of the other four groups had different changes. Leptin mRNA expression of intralipid group was significantly increased in adipose tissue but decreased in lung and liver.. Leptin expression levels may be affected by the changes of energy metabolism and neuroendocrine function after injury, which suggests a possible protective role for leptin in the recovery of body homeostasis.

Topics: Animals; Female; Inflammation; Intestinal Perforation; Leptin; Ligation; Male; Peritonitis; Rabbits; Rats; Rats, Sprague-Dawley; RNA, Messenger

Adipokines, cytokines mainly produced by adipocytes, are active participants in the regulation of inflammation. Administration of zymosan (ZY) was used to investigate the regulation and role of adipokines during peritonitis in mice. Injection of ZY led to a significant increase in leptin levels in both serum and peritoneal lavage fluid, whereas a differential trend in local vs. systemic levels was observed for both resistin and adiponectin. The role of leptin in ZY-induced peritonitis was investigated using leptin-deficient ob/ob mice, with and without reconstitution with exogenous leptin. Leptin deficiency was associated with delayed resolution of peritoneal inflammation induced by ZY, because ob/ob mice had a more pronounced cellular infiltrate in the peritoneum as well as higher and prolonged local and systemic levels of IL-6, TNFalpha, IL-10, and chemokine (C-X-C motif) ligand 2 compared with wild-type mice. Reconstitution with exogenous leptin exacerbated the inflammatory infiltrate and systemic IL-6 levels in ob/ob mice while inhibiting production of TNFalpha, IL-10, and chemokine (C-X-C motif) ligand 2. In contrast with the important role of leptin in regulating each aspect of ZY-induced peritonitis, adiponectin deficiency was associated only with a decreased inflammatory infiltrate, without affecting cytokine levels. These findings point to a complex role for adipokines in ZY-induced peritonitis and further emphasize the interplay between obesity and inflammation.

Topics: Adipokines; Adiponectin; Animals; Female; Leptin; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Neutrophil Infiltration; Obesity; Peritonitis; Resistin; Zymosan

The serum leptin level is elevated in patients undergoing peritoneal dialysis (PD) and associated with a loss of lean body mass. The nutritional status of PD patients may further be worsened following peritonitis. We investigated the association between hyperleptinaemia, inflammation and malnourishment in PD-related peritonitis.. We conducted a prospective study on PD patients who developed peritonitis. Blood samples were obtained as baseline (D0) before the onset of peritonitis, and once peritonitis developed, leptin, adiponectin (ADPN) and other inflammatory markers were collected, on day 1 (D1), day 7 (D7) and day 42 (D42) of peritonitis. Patients were followed-up for any censor event or 1 year after peritonitis.. Forty-two patients with a mean age of 62.9+/-13.2 years were recruited. Fourteen (33.3%) were diabetic. The serum leptin levels increased significantly from baseline to day 1 and 7, but fell back to the premorbid state at day 42. In contrast, the ADPN level decreased from a baseline value of 15.60+/-10.4 microg/ml to 13.01+/-8.1 microg/ml on day 1 (P=0.01) but rose to 14.39+/-8.9 microg/ml on day 7 (P=0.28) and 13.87+/-7.9 microg/ml on day 42 (P=0.21). High-sensitivity C-reactive protein (hs-CRP) increased significantly from baseline to day 1, 7 and even at day 42. The lean body mass (LBM) and nutritional markers decreased significantly after peritonitis. For patients with high hs-CRP (>3.0 mg/l) at day 42, there was a higher mortality rate than for those with lower hs-CRP (<3.0 mg/l, P=0.02), even if they were in clinical remission of peritonitis.. Our study confirmed an increase in serum leptin during acute peritonitis and a prolonged course of systemic inflammation after apparent clinical remission of peritonitis. These factors related to the persistent chronic inflammation may contribute to the development of malnourishment and poor survival rate.

Topics: Adiponectin; Aged; C-Reactive Protein; Chronic Disease; Female; Follow-Up Studies; Humans; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Peritoneal Dialysis; Peritonitis; Predictive Value of Tests; Prognosis; Prospective Studies; Protein-Energy Malnutrition; Tumor Necrosis Factor-alpha

Noninfectious complications of peritoneal dialysis (PD) are increasing in relative importance due to success in decreasing the rate of PD peritonitis. Mechanical catheter complications are emerging as an important cause of technique failure at the same time as experience with PD is declining in North America. There is also increasing interest in metabolic complications of PD and in glucose-sparing strategies to reduce the risk for hyperglycemia, hyperinsulinemia, and hyperleptinemia. This clinical commentary focuses on these noninfectious complications of PD.

Topics: Glucose; Humans; Hyperglycemia; Hyperinsulinism; Leptin; Peritoneal Dialysis; Peritonitis; Renal Dialysis; Renal Insufficiency

Both the systemic release of inflammatory mediators and activation of the neuroendocrine axis by sensory afferent nerves (SANs) have been implicated as initiators of the metabolic response to infection. In this study, we investigate the role of SANs as mediators of protein catabolism and the insulin-like growth factor (IGF) axis during abdominal sepsis using capsaicin (Cap) to selectively destroy nociceptive sensory axons.. Four groups of male Sprague-Dawley rats were studied: Control, Control+Cap, Sepsis, and Sepsis+Cap. Rats were injected with Cap (75 mg/kg) on day 1 and (50 mg/kg) on day 2 to destroy SANs. Time-matched control and septic rats were pair-fed and injected with vehicle on the same schedule. Controls underwent sham laparotomy, while septic rats had a fecal-agar pellet inoculated with Escherichia coli and Bacteroides fragilis implanted in the peritoneal cavity. Blood and tissues were harvested 5 days after the induction of sepsis. Plasma IGF-I, IGFBP-1, and -3 were measured by radioimmunoassay and Western blot analysis. IGF-I, acid-labile subunit (ALS), IGFBP-1 and -3 mRNA levels were determined by Northern blot analysis.. Mortality was 40% in septic rats vs 0% in the sepsis+Cap group. Capsaicin had no effect on muscle mass, protein content, or the IGF system in control rats. However, sepsis-induced reductions in gastrocnemius mass (25%) and protein content (35%) were ameliorated by capsaicin. The sepsis-induced decrease in hepatic IGF-I mRNA and circulating IGF-I (26%), as well as the 4-fold increase in plasma IGFBP-1 and hepatic IGFBP-1 mRNA were prevented by capsaicin.. Capsaicin-sensitive nerves mediate mortality, the catabolism of skeletal muscle, and selected elements of the IGF system during abdominal sepsis. The results suggest an important role for nociceptive SANs and the neuroendocrine system in mediating the host response to abdominal infection.

Topics: Animals; Capsaicin; Eating; Insulin; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Leptin; Male; Models, Animal; Muscle, Skeletal; Nociceptors; Peritonitis; Proteins; Rats; Rats, Sprague-Dawley

Plasma leptin and ob gene mRNA levels were increased in mice following bacterial peritonitis, and blocking an endogenous tumor necrosis factor alpha (TNF-alpha) response blunted the increase. However, plasma leptin concentrations did not correlate with the associated anorexia. We conclude that leptin expression is under partial regulatory control of TNF-alpha in peritonitis, but the anorexia is not dependent on increased leptin production.

Topics: Animals; Anorexia; Bacterial Infections; Female; Leptin; Mice; Mice, Inbred C57BL; Obesity; Peritonitis; Protein Biosynthesis; Tumor Necrosis Factor-alpha