Amelioration of experimental colitis by thalidomide.
BACKGROUND
Rectal administration of iodoacetamide induces colitis by blocking sulphhydryl groups and generating inflammatory mediators. Thalidomide, a non-barbiturate hypnotic, also has an anti-inflammatory effect, presumably by suppressing the production of tumor necrosis factor alpha. In patients with Crohn's disease, neutralization or suppression of TNF alpha reduces inflammation.


OBJECTIVE
To evaluate the effects of thalidomide in a model of experimental colitis.


METHODS
Colitis was induced in rats by intracolonic administration of 3% iodoacetamide. In the treatment group, thalidomide 50 mg/kg was given daily by gavage and continued for 7 days until the rats were sacrificed. Their colons were then processed for wet weight, lesion area, weight of mucosal scraping, myeloperoxidase activity and histology. Serum levels of TNF were determined.


RESULTS
Colonic wet weight, lesion area, myeloperoxidase activity and serum levels of TNF alpha were significantly lower (P < 0.05) in the treatment group (iodoacetamide + thalidomide) than the control group (iodoacetamide only). Histologically, colonic inflammation in the treated group was markedly decreased.


CONCLUSIONS
Thalidomide effectively decreases colitis induced by iodoacetamide. The mechanism is probably associated with inhibition of TNF alpha, and should be further studied.
Kenet
G
G
Department of Gastroenterology, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Wardi
J
J
Avni
Y
Y
Aeed
H
H
Shirin
H
H
Zaidel
L
L
Hershkoviz
R
R
Bruck
R
R
D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007460:Iodoacetamide / Q000633:toxicity; D051381:Rats; D013792:Thalidomide / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000477:Alkylating Agents; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D007460:Iodoacetamide