PubMed Health⌕ Search

PubMed · 16912557

Role of intestinal function in cachexia.

Abstract

PURPOSE OF REVIEW: Cachexia is a prominent feature in many chronic diseases, but its pathogenesis is still not fully understood. This article reviews recent research into the role of the gut barrier in the pathogenesis of inflammation and cachexia with special emphasis on two potentially catabolic diseases: liver cirrhosis and chronic heart failure. RECENT FINDINGS: There is increasing evidence that catabolic diseases such as liver cirrhosis and chronic heart failure are associated with increased gut permeability, endotoxemia and enhanced expression of proinflammatory cytokines. In liver cirrhosis normalization of portal hypertension by insertion of a transjugular intrahepatic portosystemic stent shunt obviously causes improvement not only of gut barrier function, but also of nutritional status. SUMMARY: Although its pathogenesis is not yet completely understood, proinflammatory cytokines have been implicated in the onset and progression of cachexia. Recent data support the hypothesis that impaired gut barrier function and increased permeability further translocation of endotoxins. Increased endotoxemia might be a potent trigger of systemic inflammatory response which is involved in the pathogenesis of the cachexia syndrome. Thus, it is tempting to speculate that therapeutic strategies for the improvement of gut barrier function will concomitantly improve nutritional status.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Matthias Pirlich, Kristina Norman, Herbert Lochs, Jürgen Bauditz. 2006. Role of intestinal function in cachexia.. https://doi.org/10.1097/01.mco.0000241671.09676.d8

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Pathophysiology of glutamine and glutamate metabolism in premature infants.

PURPOSE OF REVIEW: The potential efficacy of glutamine and glutamate as nutritional supplements for premature infants was originally met with enthusiasm. Despite no evidence of toxicity in the clinical trials, the use of glutamine has not become routine. In certain studies, the benefits seem clear, whereas in others, benefits have not been demonstrated. Specific designs for studies have been difficult, targets based on mechanistic frameworks have been poorly defined, study populations are heterogeneous and putative mechanisms of glutamine action are multifold. Our purpose is to review recent findings pertaining to (1) the action and mechanisms of glutamine and glutamate in the gastrointestinal tract, and (2) the future directions for glutamine and glutamate research with a focus on the premature neonate. RECENT FINDINGS: Studies elucidating mechanisms of glutamine action include tissue protection, immune modulation, preservation of glutathione and antioxidant capacity, preservation of metabolism, decreased intestinal apoptosis, and enhancement of heat shock proteins. The ability to decrease gastrointestinal-derived systemic inflammation appears to have especially significant implications for premature infants. SUMMARY: We review recent studies of mechanisms of glutamine and glutamate action, pertinent clinical trials, and suggest areas for future research based on these mechanisms.

Bacterial Translocation↗

Phosphatidylinositol 3'-kinase is a critical mediator of interferon-gamma-induced increases in enteric epithelial permeability.

The epithelial lining of mucosal surfaces acts as a barrier to regulate the entry of antigen and pathogens. Nowhere is this function of the contiguous epithelium more important than in the gut, which is continually exposed to a huge antigenic load and, in the colon, an immense commensal microbiota. We assessed the intracellular signaling events that underlie interferon (IFN) gamma-induced increases in epithelial permeability using monolayers of the human colonic T84 epithelial cell line. Confluent epithelial monolayers on semipermeable supports were treated with IFNgamma (20 ng/ml), and barrier function was assessed 48 h later by measuring transepithelial electrical resistance (TER: reflects passive ion flux), fluxes of (51)Cr-EDTA and horseradish peroxidase (HRP), and transcytosis of noninvasive, nonpathogenic Escherichia coli (strain HB101). Exposure to IFNgamma decreased barrier function as assessed by all four markers. The phosphatidylinositol 3'-kinase (PI-3K) inhibitors, LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride] and wortmannin, did not affect baseline permeability characteristics but completely blocked the drop in TER, increased fluxes of (51)Cr-EDTA and HRP, and significantly reduced E. coli transcytosis evoked by IFNgamma. In addition, use of the pan-protein kinase C (PKC) inhibitor, bisindolylmaleimide I (5 muM), but not rottlerin (blocks PKCdelta), partially ameliorated the drop in TER and inhibited increased E. coli transcytosis. Addition of the PI-3K and PKC inhibitors to epithelia 6 h after IFNgamma exposure still prevented the increase in paracellular permeability but not E. coli transcytosis. Thus, IFNgamma-induced increases in epithelial paracellular and transcellular permeability are critically dependent on PI-3K activity, which may represent an epithelial-specific target to treat immune-mediated loss of barrier function.

Bacterial Translocation↗

Differences in invasion and translocation of Burkholderia cepacia complex species in polarised lung epithelial cells in vitro.

In order to investigate the mechanisms by which Burkholderia cepacia complex (Bcc) strains cross the epithelial barrier of the lung and cause septicaemia in a subgroup of Cystic Fibrosis (CF) patients, the invasiveness of four Bcc species have been examined in three lung epithelial cells: A549, 16HBE14o- and Calu-3. The latter two cell lines form polarised monolayers when grown on filters. Invasion of both cell lines by B. multivorans strains was reduced when the cells were grown as tight monolayers compared unpolarised cells, suggesting basolateral receptors are required for the process. In contrast, four B. cenocepacia strains showed comparable invasion of both cell lines irrespective of culture model. All four species of Bcc reduced the TER of Calu-3 monolayers. However, while B. cepacia, B. multivorans and B. stabilis strains readily translocated across the epithelial monolayer, B. cenocepacia translocation was slower. Both B. multivorans and B. cenocepacia altered expression of ZO-1 in Calu-3 cells, but not E-cadherin. Overall, the findings that Bcc strains from four species, which differ greatly in their virulence, have the potential to disrupt tight junctions and to translocate across the epithelium, demonstrates this effect is not exclusive to the most virulent species.

Bacterial Translocation↗