Rectal Nitric Oxide Gas and Stool Cytokine Levels during the Course of Infectious Gastroenteritis

Abstract

Nitric oxide (NO) is known to be an important inflammatory mediator with a potential role in gastrointestinal diseases. We prospectively studied the luminal NO levels in 51 patients with infectious gastroenteritis, 35 patients with nonenteric bacterial infections, and 11 healthy control subjects. The levels of proinflammatory cytokines were simultaneously measured in the stools of patients with gastroenteritis. Rectal gas was sampled with balloon catheters made of silicone and was analyzed for NO levels by chemiluminescence. The median rectal NO level was 2,450 ppb in the acute phase of gastroenteritis and gradually decreased to 225 ppb after 3 to 8 weeks, whereas the median NO values were 150 ppb in patients with nonenteric bacterial infections and 100 ppb in healthy control subjects. Patients with Salmonella, Shigella, and Campylobacter infections generally had more severe symptoms and a higher median NO level (17,250 ppb) than patients with Clostridium difficileassociated diarrhea (median NO value, 275 ppb). Interleukin-1␤ levels were elevated in 82% of the patients at disease onset and decreased during the convalescent phase. In contrast, gamma interferon was detected in only 16% of the patients and was predominantly collected in stool samples collected during the subacute and convalescent stages. Our data point to the possibility of using this easy, minimally invasive method for luminal NO measurement as a diagnostic tool, among others, to evaluate the degree of intestinal inflammation in patients with infectious gastroenteritis.

Redox sensor SsrB Cys 203 enhances Salmonella fitness against nitric oxide generated in the host immune response to oral infection

“…The nitrosative chemistry generated by acidified NO 2 − not only inhibits SPI2 expression (13) but also, as shown herein, S-nitrosylates SsrB. The advantage of Salmonella expressing the wild-type, RNS-responsive ssrB allele is evident in mice on an NRAMP1 R background, indicating that sensing of RNS by Cys 203 must take place within macrophages where the NRAMP1 metal transporter is expressed (26).…”

“…This rich biochemistry probably mediates the broadspectrum antimicrobial activity of reactive nitrogen species (RNS) against phylogenetically diverse microorganisms (1). Diarrheagenic Salmonella elicit a burst of NO in rectal content in infected humans (2) and stimulate the accumulation of iron-nitrosyl adducts in affected viscera of experimental animals (3). Mounting evidence indicates that these RNS are not mere signatures of the infection but are active components of the anti-Salmonella host arsenal.…”

“…Two molecules of HNO 2 in turn condensate to form the strong oxidative and nitrosative species N 2 O 3 . Acidified NO 2 − is a relevant source of nitrosative stress in our system because it adds to the RNS of Salmonella-infected macrophages (14). Strain AV07104 expressing an SsrB::3xFLAG was cultured for 6 h in EG medium, pH 5.5, containing 750 μM NO 2 − or NO 3 − .…”

Diagnosis of Clostridium difficile Infection: an Ongoing Conundrum for Clinicians and for Clinical Laboratories

“…There are no commercial assays available for measuring cytokine levels in fecal specimens. Some investigators have shown the correlation of elevated levels of IL-1␤ and IL-8 in active disease, particularly in cases of moderate to severe infection (162,166,167), with subsequent decreases in levels of these cytokines in stool when the patient recovers from acute infection (166). In a study by Jiang et al, the authors demonstrated that a single-nucleotide polymorphism (SNP) (251 A/A) in the IL-8 gene is associated with increased susceptibility to C. difficile disease (167).…”

Campylobacter jejuni-Induced Cytokine Responses in Avian Cells

“…Campylobacter can invade human epithelial cell monolayers (11,12), causing disruption to the epithelium and gaining access to its basal side (41,45). Interleukin-1␤ (IL-1␤), IL-8, and nitric oxide (NO) are produced during human Campylobacter infections (10), and in vitro experiments with human-derived epithelial cell lines have shown that C. jejuni can induce the secretion of a range of cytokines and chemokines (2,3,16,17,19).…”