Effects of octreotide treatment on early TNF-alpha production and localization in experimental chronic colitis.
BACKGROUND
Colitis induced by trinitrobenzene sulphonic acid (TNB) is a model of Th1 disease, mainly explored from the third day of induction. It has recently been shown that octreotide and other somatostatin analogues can modify inflammatory/immune processes by acting on cytokines.


OBJECTIVE
To examine TNFalpha production and the effect of preventive treatment with octreotide, during the early phase of TNB-colitis.


METHODS
Thirty milligrams TNB with 50% ethanol was instilled into the colon of male Wistar rats. Treated groups received octreotide (2x10 microg x day/rat) or dexamethasone (1x2 mg x day/kg), subcutaneously, with the first injection before TNB. Eight and 80 h later, the colon was excised and processed for histology, TNFalpha immunohistochemistry, quantification of cytokine release ex vivo and tissue-inducible NO synthase (iNOS) activity.


RESULTS
Maximal TNFalpha production was observed at the 8th hour, associated with intense immunostaining of the external muscle layer. Octreotide treatment decreased TNFalpha expression (staining and activity) and iNOS activity. At the 80th hour, submucosal macrophages were positive for TNFalpha and colonic production of IL1beta and interferon gamma was increased; all these effects were reduced by octreotide treatment.


CONCLUSIONS
TNFalpha was expressed early by resident muscle cells, before staining of infiltrated immune cells and increased production of interferon gamma. TNFalpha regulation by octreotide suggests that this drug might exert anti-inflammatory properties via smooth muscle cells.
Lamrani
A
A
Department of Pharmacology, CNRS 1534, Paris, France; Laboratoire de recherche en pathologie digestive and Division of Gastroenterology, Paris, France.
Tulliez
M
M
Chauvelot-Moachon
L
L
Chaussade
S
S
Mauprivez
C
C
Hagnéré
A M
AM
Vidon
N
N
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002908:Chronic Disease; D003092:Colitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D015282:Octreotide / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*
D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D003907:Dexamethasone; D015282:Octreotide