Tumour necrosis factor alpha changes porcine intestinal ion transport through a paracrine mechanism involving prostaglandins.

Kandil, Hossam M.; Berschneider, Helen M.; Argenzio, Robert A.

doi:10.1136/gut.35.7.934

Cited by 80 publications

(43 citation statements)

References 38 publications

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“…In addition, we observed an association between the overproduction of TNF-␣ and more diarrheal episodes in patients with rotavirus infection, although the mechanism for this relationship is unknown. It could be due to the ability of TNF-␣ to induce increased levels of Cl Ϫ secretion in intestinal epithelial cells, as has been reported for patients with other infections or inflammatory processes (21,31). We could not identify cytokines that might mediate the expression or severity of vomiting.…”

Section: Discussionmentioning

confidence: 42%

Cytokines as Mediators for or Effectors against Rotavirus Disease in Children

Jiang

Snipes-Magaldi

Dennehy

et al. 2003

Clin Vaccine Immunol

125

104

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Rotavirus is the most common cause of severe gastroenteritis in young children, but the pathogenesis and immunity of this disease are not completely understood. To examine the host response to acute infection, we collected paired serum specimens from 30 children with rotavirus diarrhea and measured the levels of nine cytokines (interleukin-1␤ [IL-1␤], IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, gamma interferon [IFN-␥], and tumor necrosis factor alpha [TNF-␣]) using a microsphere-based Luminex Flowmetrix system. Patients with acute rotavirus infection had elevated median levels of seven cytokines in serum, and of these, the levels of three (IL-6, IL-10, and IFN-␥) were significantly (P < 0.05) higher than those in serum from control children without diarrhea. Patients with fever had significantly (P < 0.05) higher levels of IL-6 in serum than control children, and those with fever and more episodes of diarrhea had significantly (P < 0.05) higher levels of TNF-␣ than those without fever and with fewer episodes of diarrhea. We further demonstrated a negative association (P < 0.05) between the levels of IL-2 and the number of stools on the day on which the first blood sample was collected. Finally, patients with vomiting had significantly (P < 0.05) lower levels of IFN-␥ than those without vomiting. Our pilot study provides evidence that the types and magnitudes of cytokine responses to rotavirus infection in children influence or reflect the clinical outcome of disease. These findings suggest that certain cytokines may play an important role in the pathogenesis of and the protection against rotavirus disease in children and, consequently, may provide directions and insights that could prove critical to the prevention or treatment of this important disease.

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Section: Discussionmentioning

confidence: 42%

Cytokines as Mediators for or Effectors against Rotavirus Disease in Children

Jiang

Snipes-Magaldi

Dennehy

et al. 2003

Clin Vaccine Immunol

125

104

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“…Cryptosporidium infection results in intestinal structural and physiologic changes such as reduced glucose-NaCl absorption, increased chloride anion secretion (Cl Ϫ ), and epithelial barrier disruption (10,12,17,18). These alterations are known to lead to the pathogenesis of cryptosporidiosis, which includes dehydration, weight loss, diarrhea, and malabsorption.…”

mentioning

confidence: 99%

Substance P Is Responsible for Physiological Alterations Such as Increased Chloride Ion Secretion and Glucose Malabsorption in Cryptosporidiosis

et al. 2007

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Cryptosporidiosis, caused by the protozoan parasite Cryptosporidium, causes self-limited diarrhea in immunocompetent hosts and severe life-threatening diarrhea in AIDS patients. Highly active antiretroviral therapy has been used to effectively treat cryptosporiosis in some but not all AIDS patients. Therefore, there is an urgent need for innovative drugs to treat this disease. Cryptosporidium infection results in intestinal pathophysiological changes such as glucose malabsorption, increased chloride ion (Cl ؊ ) secretion, and epithelial barrier disruption, leading to disease pathogenesis. In order to develop tools to combat this opportunistic pathogen, it is vital to understand mediators involved in disease pathogenesis. Substance P (SP), a neuropeptide and pain transmitter, is located in the gastrointestinal tract. SP can cause Cl ؊ secretion in human gastrointestinal explants. However, its role in cryptosporidiosis has not been fully studied. Jejunal samples from macaques before and after Cryptosporidium parvum infection were assayed for SP and SP receptor mRNA and protein levels by reverse transcription-PCR and by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. The role of SP in pathophysiological alterations, such as Cl ؊ secretion and glucose malabsorption, was studied using tissues derived from macaques infected with C. parvum by the Ussing chamber technique. SP and SP receptor mRNA and protein expression levels were increased in jejunal samples following C. parvum infection and were accompanied by increased basal ion secretion and glucose malabsorption. In vitro treatment of samples obtained from infected macaques with the SP receptor antagonist aprepitant (Emend; Merck, Whitehouse Station, NJ) completely reversed the increase in basal ion secretion and corrected the glucose malabsorption. Our findings raise the possibility of using SP receptor antagonists for the treatment of symptoms associated with cryptosporidiosis.

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“…Lamina propria macrophages (LPMs) in the intestinal mucosa of patients with Crohn disease and ulcerative colitis are activated (24,25). Activation of LPMs results in the release of tumor necrosis factor ␣ (TNF␣) and other mediators that can directly stimulate intestinal ion transport (26,27), suggesting a role for these cells in the pathophysiology of inflammatory diarrhea. A number of recent studies have indicated that SP and its receptor may be important in the modulation and amplification of macrophage function.…”

mentioning

confidence: 99%

Increased substance P responses in dorsal root ganglia and intestinal macrophages duringClostridium difficiletoxin A enteritis in rats

Castagliuolo

Keates

Qiu

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

153

124

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Previously we reported that pretreatment of rats with the substance P (SP) antagonist CP-96,345 inhibits the enterotoxic responses following administration of toxin A from Clostridium difficile into ileal loops, indicating that SP participates in the intestinal responses to this toxin. We now report that injection of toxin A into rat ileum causes a rapid increase in SP content in lumbar dorsal root ganglia (DRG) and mucosal scrapings 30-60 min after toxin A administration. Toxin A-mediated f luid secretion, mannitol permeability, and ileal histologic damage is significantly increased only after 2 hr. Toxin A also causes an increase in the abundance of SP mRNA in lumbar DRG and ileal mucosa as measured by reverse transcription-PCR. Lamina propria macrophages (LPMs) obtained from toxin A-injected loops release greater amounts of tumor necrosis factor ␣ (TNF␣) and SP as compared with LPMs isolated from buffer-injected loops (P < 0.01). Pretreatment of rats with the SP antagonist CP-96,345 inhibits toxin A-mediated TNF␣ release from isolated LPMs, whereas an inactive enantiomer (CP-96,344) of the SP antagonist has no effect. LPMs obtained from toxin A-injected ileal loops incubated in vitro with SP (10 ؊8 to 10 ؊9 M) show enhanced TNF␣ secretion, whereas LPMs isolated from buffer-injected loops do not respond to SP. In addition, LPMs obtained from toxin A-injected ileal loops incubated in vitro with CP-96,345 showed a diminished TNF␣ release. Our results indicate that activated LPMs secrete SP during toxin A enteritis that can lead to secretion of cytokines, suggesting an autocrine͞paracrine regulation of cytokine secretion by SP from LPMs during intestinal inf lammation.Substance P (SP), an 11-aa peptide member of the tachykinin family originally isolated by Chang and Leeman (1), is a peptide distributed throughout the central and peripheral nervous system. In the intestine, SP has been found in capsaicin-sensitive sensory neurons (2), enteric neurons (3), as well as intestinal enteroendocrine cells (4). SP is also synthesized in the cell bodies of the dorsal root ganglia (DRG) (5), and evidence indicates that release of SP from DRG to spinal cord mediates nociceptive and inflammatory stimuli (6-8). Recently, Reinshagen et al. (9) reported decreased levels of SP in the DRG of rabbits 48 hr after induction of colitis, suggesting that SP may be released from sensory neurons during the acute phase of inflammation. However, there are no studies specifically evaluating the SP content in the DRG during acute intestinal inflammation mediated by bacterial enterotoxins.In addition to its role as a neurotransmitter, SP also participates in immune and inflammatory responses. Mast cells (10), polymorphonuclear leukocytes (11), T lymphocytes (12, 13), and macrophages (14) can respond to SP, indicating that the effects of SP during inflammation may be mediated by direct activation of these cells. SP levels are also elevated in inflamed tissues (15-17), and increased binding sites for SP have been demonstrated at sites o...

show abstract

Tumour necrosis factor alpha changes porcine intestinal ion transport through a paracrine mechanism involving prostaglandins.

Cited by 80 publications

References 38 publications

Cytokines as Mediators for or Effectors against Rotavirus Disease in Children

Cytokines as Mediators for or Effectors against Rotavirus Disease in Children

Substance P Is Responsible for Physiological Alterations Such as Increased Chloride Ion Secretion and Glucose Malabsorption in Cryptosporidiosis

Increased substance P responses in dorsal root ganglia and intestinal macrophages duringClostridium difficiletoxin A enteritis in rats

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