ABSTRACT
Morbid obesity is associated with low-grade systemic inflammation and immune activation. Thereby various pro-inflammatory cytokines like TNF-alpha, IL-1, IL-6, IFN-gamma and hormones, such as leptin are synthesized and released in human adipose tissue. The immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) is widely distributed in mammals and is inducible preferentially by IFN-gamma. IDO degrades the essential amino acid tryptophan to form N-formyl kynurenine which, depending on cell type and enzymatic repertoires, is subsequently converted to finally form niacin. More recently, it has been proposed that activation of IDO is also critically involved in the regulation of immune responses. In obesity plasma tryptophan concentrations have been shown to be decreased and to be independent of weight reduction or dietary intake. In addition, we previously demonstrated that IDO mediated tryptophan catabolism due to chronic immune activation is the cause for such reduced tryptophan plasma levels in morbidly obese patients compared to lean individuals. Furthermore, these tryptophan metabolic changes may subsequently reduce serotonin production and cause mood disturbances, depression, and impaired satiety ultimately leading to increased caloric uptake and obesity. IDO-mediated tryptophan degradation due to chronic immune activation can therefore be considered as the driving force for food intake. We here review the potential pathogenic links between chronic immune activation and decreased IDO mediated tryptophan and serotonin levels in morbid obesity.
Subject(s)
Indoleamine-Pyrrole 2,3,-Dioxygenase/immunology , Obesity, Morbid/immunology , Adipose Tissue/immunology , Adipose Tissue/metabolism , Animals , Bariatric Surgery , Ghrelin , Humans , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Leptin/metabolism , Macrophages/immunology , Obesity, Morbid/metabolism , Obesity, Morbid/surgery , Peptide Hormones/metabolism , Serotonin/metabolism , Substance-Related Disorders/metabolism , Tryptophan/immunology , Tryptophan/metabolism , Weight LossSubject(s)
Gram-Negative Bacterial Infections/microbiology , Ralstonia pickettii/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cystic Fibrosis/complications , Drug Resistance, Bacterial , Female , Humans , Immunocompromised Host , Infant , Male , Middle Aged , Ralstonia pickettii/drug effectsABSTRACT
Continuous ambulatory peritoneal dialysis (CAPD) lavage can be interpreted as an artificial short-term ascites. The cellular content of 362 CAPD specimens from 32 patients was investigated. Irregular inflammatory reactions were seen in 85.3% of the specimens and eosinophilia in 27.6%. Mesothelial aggregates of great variability were registered in 59.4% of the specimens and mainly atypical mitoses in 7.5%. The cytologic changes seen in those patients from whom lavage fluids were examined over 10 to 12 months did not correlate with the changes in blood chemistry (BUN and creatinine) in those cases.
