Pro-inflammatory effects of cholera toxin: Role of tumor necrosis factor alpha

C. F G Viana, D. H. Melo, B. A. Carneiro-Filho, M. A. Michelin, G. A C Brito, F. Q. Cunha, A. A M Lima, R. A. Ribeiro*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Cholera toxin has been traditionally described as the one that does not induce inflammation. It has, however, potent adjuvant and immuno-modulatory activities. Since the adjuvanticity of other compounds is linked to their capacity to induce inflammation, in the present study the pro-inflammatory activity of cholera toxin was investigated. We studied this activity in the following rat models of inflammation: paw edema and neutrophil migration into the peritoneal cavity, and evaluated cholera toxin's effect on tumor necrosis factor alpha (TNF-α) production by mouse macrophages. We, also, explored the effects of dexamethasone (DEXA) and of two inhibitors of TNF-α production, thalidomide (TAL) and pentoxifylline, on paw swelling. Cholera toxin-induced significant and dose-dependent paw edema, which peaked 48h after toxin challenge (Cholera toxin2.5μg: 2.39±0.22ml). Cholera toxin B subunit did not show edematogenic activity. DEXA, TAL and pentoxifylline significantly reduced cholera toxin-induced edema (DEXA0.5mg/kg: 42.6% of inhibition; TAL45mg/kg: 36% of inhibition; pentoxifylline 45mg/kg: 61% of inhibition). Neither cholera toxin nor its B subunit induced neutrophil migration into peritoneal cavities. Cholera toxin stimulated the release of TNF-α by macrophages (cholera toxin10μg: 11.46±0.44UI/ml). These data provide evidences that cholera toxin exhibits significant pro-inflammatory activity. It also indicates the role of TNF-α upon the pathophysiology of this event based on the inhibitory action of DEXA, TAL and pentoxifylline, and on TNF-α secretion induced by cholera toxin.

Original languageEnglish (US)
Pages (from-to)1487-1494
Number of pages8
JournalToxicon
Volume40
Issue number10
DOIs
StatePublished - Oct 1 2002

Keywords

  • Cholera toxin
  • Inflammation
  • Tumor necrosis factor
  • Vibrio cholerae

ASJC Scopus subject areas

  • Toxicology

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