Therapeutic effects of vasoactive intestinal peptide in the trinitrobenzene sulfonic acid mice model of Crohn's disease.
OBJECTIVE
Crohn's disease (CD) is a chronic debilitating disease of unknown etiology that is characterized by severe inflammation of the colon. Vasoactive intestinal peptide (VIP) has recently emerged as a promising candidate for treatment of inflammatory Th1-driven diseases. We studied the effect of VIP in trinitrobenzene sulfonic acid (TNBS)-induced colitis, which has clinical and molecular features in common with CD.


METHODS
A 3-mg enema of TNBS was given to BALB/c mice, and VIP (1 nmol) was given either as a single dose at 12 hours or every other day. Weight loss, histopathology, and chemokine and cytokine levels in serum and colon extracts were assessed. VIP was also tested given 5 days after the onset of TNBS-induced colitis, and its effect was analyzed given a second dose of TNBS.


RESULTS
Treatment with VIP reduced the clinical and histopathologic severity of TNBS-induced colitis, abrogating body weight loss, diarrhea, and macroscopic and microscopic intestinal inflammation. The therapeutic effects of VIP were associated with down-regulation of both inflammatory and Th1-driven autoimmune responses, including tumor necrosis factor alpha, interleukin 1, and interleukin 6 in colon extracts and serum as well as interferon gamma by splenic and lamina propria CD4(+) T cells. VIP reduced disease severity when given after disease onset and dramatically reduced disease recurrence given a second dose of TNBS.


CONCLUSIONS
Our data suggest that VIP has beneficial prophylactic and therapeutic effects in TNBS-induced colitis and is a promising candidate to test for potential benefits in CD.
Abad
Catalina
C
Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain.
Martinez
Carmen
C
Juarranz
Maria G
MG
Arranz
Alicia
A
Leceta
Javier
J
Delgado
Mario
M
Gomariz
Rosa P
RP
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D003424:Crohn Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000276:immunology; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018005:Receptors, Vasoactive Intestinal Peptide / Q000378:metabolism; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D019282:Wasting Syndrome / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology
D016207:Cytokines; D005765:Gastrointestinal Agents; D018005:Receptors, Vasoactive Intestinal Peptide; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide; D014302:Trinitrobenzenesulfonic Acid