Pro-inflammatory effects of cholera toxin: role of tumor necrosis factor alpha.
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-alpha) production by mouse macrophages. We, also, explored the effects of dexamethasone (DEXA) and of two inhibitors of TNF-alpha production, thalidomide (TAL) and pentoxifylline, on paw swelling. Cholera toxin-induced significant and dose-dependent paw edema, which peaked 48 h after toxin challenge (Cholera toxin(2.5 microg): 2.39 +/- 0.22 ml). Cholera toxin B subunit did not show edematogenic activity. DEXA, TAL and pentoxifylline significantly reduced cholera toxin-induced edema (DEXA(0.5 mg/kg): 42.6% of inhibition; TAL(45 mg/kg): 36% of inhibition; pentoxifylline (45 mg/kg): 61% of inhibition). Neither cholera toxin nor its B subunit induced neutrophil migration into peritoneal cavities. Cholera toxin stimulated the release of TNF-alpha by macrophages (cholera toxin(10 microg): 11.46 +/- 0.44 UI/ml). These data provide evidences that cholera toxin exhibits significant pro-inflammatory activity. It also indicates the role of TNF-alpha upon the pathophysiology of this event based on the inhibitory action of DEXA, TAL and pentoxifylline, and on TNF-alpha secretion induced by cholera toxin.
D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002772:Cholera Toxin / Q000633:toxicity*; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D010431:Pentoxifylline / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013792:Thalidomide / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014734:Vibrio cholerae / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D003907:Dexamethasone; D002772:Cholera Toxin; D010431:Pentoxifylline