Inflammatory mediators and immune function are altered in home parenteral nutrition patients

Hise, Mary; Compher, Charlene; Harlan, Lisa M.; Kohlmeier, Jacob E.; Benedict, Stephen H.; Gajewski, Byron; Brown, John C.

doi:10.1016/j.nut.2005.05.011

Cited by 18 publications

(11 citation statements)

References 23 publications

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“…3, we speculate that the flagellin and LPS seen by the gut-associated immune system in our patients may have occurred as a result of low-level, intermittent bacterial translocation across the gut mucosa. There were no statistically significant differences in anti-flagellin IgM, IgA, or IgG titers in SBS patients who had serum positive for flagellin at any of the seven serial serum sample time points (baseline and weeks 4,8,12,16,20, and 24) compared with anti-flagellin titers in SBS patients without any of the serum samples positive for flagellin (not shown). Similarly, there were no statistically significant differences in anti-LPS IgM, IgA, or IgG titers in SBS patients with any serum sample positive for LPS compared with patients without any positive serum samples for LPS (not shown).…”

Section: Discussionmentioning

confidence: 93%

“…Univariate linear regression analysis was used to analyze SBS patient data for the influence of age, residual small bowel length, percent residual colon, time since last bowel resection, and time on PN on baseline flagellin-and LPS-specific IgM, IgA, and IgG levels. Univariate linear regression was also used to relate the weekly PN requirement at baseline and weeks 12,20, and 24 to flagellin-and LPS-specific IgM, IgA, and IgG levels at these time points. P values Յ0.05 were considered statistically significant.…”

Section: Methodsmentioning

confidence: 99%

“…At the end of study week 4, the SBS patients were discharged home; weaning from PN was commenced and oral diet adjusted and advanced as tolerated using standardized methods (7,31). The subjects returned to the GCRC at weeks 8,12,16,20, and 24 for clinical evaluation and repeat studies. All subjects had a repeat colonoscopy with biopsies as per the baseline period at weeks 4 and 12.…”

Section: Sbs Study Protocolmentioning

confidence: 99%

“…All subjects had a repeat colonoscopy with biopsies as per the baseline period at weeks 4 and 12. Serum samples were obtained from all SBS patients at baseline and at study weeks 4,8,12,16,20, and 24 visits for analysis of flagellin-and LPS-specific end points.…”

Section: Sbs Study Protocolmentioning

confidence: 99%

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Detectable serum flagellin and lipopolysaccharide and upregulated anti-flagellin and lipopolysaccharide immunoglobulins in human short bowel syndrome

Ziegler

Luo²,

Estívariz³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

100

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DP, Gewirtz AT. Detectable serum flagellin and lipopolysaccharide and upregulated anti-flagellin and lipopolysaccharide immunoglobulins in human short bowel syndrome. Am J Physiol Regul Integr Comp Physiol 294: R402-R410, 2008. First published November 14, 2007 doi:10.1152/ajpregu.00650.2007.-Gut barrier dysfunction may occur in short bowel syndrome (SBS). We hypothesized that systemic exposure to flagellin and lipopolysaccharide (LPS) in SBS might regulate specific immune responses. We analyzed serial serum samples obtained from parenteral nutrition (PN)-dependent patients with SBS versus non-SBS control serum. Serum from 23 adult SBS patients was obtained at baseline and 4, 8, 12, 16, 20, and 24 wk in a trial of modified diet with or without growth hormone. Control serum was obtained from 48 healthy adults and 37 adults requiring PN during critical illness. Serum flagellin was detected by an ELISA recognizing an array of gram-negative flagellins, and LPS was detected by limulus assay. Serum flagellin-and LPS-specific immunoglobulin levels (IgM, IgA, and IgG) were determined by ELISA. Serum flagellin and LPS were undetectable in control subjects. In contrast, serum flagellin, LPS, or both were detected in 14 SBS patients (61%) during one or more time points [flagellin alone, 5/23 (22%); LPS alone, 6/23 (26%); or flagellin ϩ LPS, 3/23 (13%)]. Flagellin-specific serum IgM, IgA, and IgG levels were markedly increased in SBS patients compared with both control populations and remained elevated during the 6-mo study period. LPS-specific IgA was significantly higher in SBS patients compared with healthy controls; LPS-specific IgM, IgA, and IgG levels each decreased over time in association with PN weaning. We conclude that adults with PN-dependent SBS are systemically exposed to flagellin and LPS, presumably from the gut lumen. This likely regulates innate and adaptive immune responses to these specific bacterial products. parenteral nutrition; intestinal barrier function SHORT BOWEL SYNDROME (SBS) occurs after massive small bowel resection and is an important clinical entity, with significant morbidity and mortality (13,36). SBS is characterized by chronic diarrhea and malabsorption, dehydration and malnutrition, and, in patients requiring parenteral nutrition (PN), frequent infections (13,36). Unfortunately, SBS and PN administration are each associated with infection by enteric gramnegative bacteria, suggesting that failure of the gut barrier occurs (2,4,5,18,20,22,24,25,33,34).

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Section: Discussionmentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Sbs Study Protocolmentioning

confidence: 99%

Section: Sbs Study Protocolmentioning

confidence: 99%

See 2 more Smart Citations

Detectable serum flagellin and lipopolysaccharide and upregulated anti-flagellin and lipopolysaccharide immunoglobulins in human short bowel syndrome

Ziegler

Luo²,

Estívariz³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

100

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“…Recently, it has been demonstrated that parenteral nutrition may result in abnormal Tlymphocyte function. 22) Therefore, we speculated that these parenterally fed, peritonitic rats might be adapted to the inflammatory stress or have immune dysfunction; thereby there were no further increased circulating NO and TNF-a in these peritonitic rats. Future studies should focus on the immune function of this subacute peritonitic rat model.…”

Section: Discussionmentioning

confidence: 96%

Dose Effects of Chronically Infused Nitric Oxide Synthase Inhibitor NG-Nitro-L-arginine Methyl Ester on Anabolic Response and Arginine Metabolism in Rats with Subacute Peritonitis

Hsiao

Lee

Tsao

et al. 2011

Biological & Pharmaceutical Bulletin

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Patients with peritonitis develop arginine deficiency due to decreased consumption, impaired absorption, and increased utilization of arginine.1,2) Arginine, a precursor for the synthesis of nitric oxide (NO), urea, creatinine, glutamate, proline, and polyamines, is a conditionally essential amino acid in stressed conditions, especially in inflammation. 1,3,4) Green et al. 5) was the first research group to show that nitrate/nitrite concentrations and the severity of infection are closely correlated. Subsequent studies showed that patients with peritonitis have uncontrolled activation of inducible nitric oxide synthase (NOS), which results in NO overproduction and the following sepsis.6) Therefore, inhibition of NOS might be a useful strategy to treat arginine deficiency and inhibit excess NO production. 6,7) In animal and human studies, the results of NOS inhibition in inflammation have been ambiguous. For example, N G -nitro-L-arginine methyl ester (L-NAME), a nonselective NOS inhibitor which inhibits both constitutive and inducible NOS, effectively ameliorated the inflammatory lesions in the skin of zinc-deficient rats, 8) improved the myocardial function in sepsis, 9) and attenuated the lipopolysaccharide-induced peritoneal permeability and NO release in mice.10) On the contrary, some studies have shown that L-NAME may cause hypertension, augment the expressions of interferon (IFN)-g and interleukin (IL)-2, and result in markedly severe disease in rats with T cell-dependent autoimmune interstitial nephritis.11) The adverse effects of NOS inhibitors have also been observed in subjects with hemodynamic instability and sepsis. [12][13][14] Evidence suggests that the therapeutic effects of NOS inhibitors may depend on the dose, timing, and the severity and category of diseases.In clinical practice, a number of in hospital patients with subacute peritonitis developed chronic malnutrition and inflammation. Administration of total parenteral nutrition solution is an efficient method to supply all daily nutrition requirements; however, it is associated with occurrence of increased complicated infections.15) Zheng et al. 16) indicated that long-term parenteral nutrition-induced liver steatosis may be attenuated by L-NAME administration. Up to now, only few reports have described the long-term application of L-NAME for subacute peritonitis. Additionally, no study has ever addressed the effects of L-NAME on the inflammatory response and amino acid metabolism in subjects administered parenteral nutrition. In our study, we used a rat model with subacute peritonitis induced by cecal puncture and administered total parenteral nutrition solution to provide adequate nutrition, and we investigated the dose effects of parenterally supplemented L-NAME on the anabolism, inflammatory response, and arginine-derived metabolites such as the intermediates of the urea cycle, circulating profile of amino acids, NO, and cytokines. MATERIALS AND METHODS Animals and Experimental DesignMale Wistar rats (8-9 weeks old), initially weighi...

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Metabolic Bone Disease in Gastrointestinal Illness

Williams¹,

Seidner²

2007

Gastroenterology Clinics of North America

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Inflammatory mediators and immune function are altered in home parenteral nutrition patients

Cited by 18 publications

References 23 publications

Detectable serum flagellin and lipopolysaccharide and upregulated anti-flagellin and lipopolysaccharide immunoglobulins in human short bowel syndrome

Detectable serum flagellin and lipopolysaccharide and upregulated anti-flagellin and lipopolysaccharide immunoglobulins in human short bowel syndrome

Dose Effects of Chronically Infused Nitric Oxide Synthase Inhibitor NG-Nitro-L-arginine Methyl Ester on Anabolic Response and Arginine Metabolism in Rats with Subacute Peritonitis

Metabolic Bone Disease in Gastrointestinal Illness

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