TNF[alpha] blockade prevents the development of inflammatory bowel disease in HLA-B27 transgenic rats

Rats transgenic for HLA-B27 and human β2microglobulin (B27TR) develop a multi-systemic disease resembling inflammatory bowel disease (IBD) and spondyloarthritis. TNFα has a crucial role in chronic inflammation. Our objective was to evaluate the effect of anti-TNFα treatment on spontaneous IBD in B27...

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Bibliographic Details
Published in:Journal of cellular and molecular medicine 2009-01, Vol.13 (1), p.164
Main Authors: Milia, Anna Franca, Manetti, Mirko, Generini, Sergio, Polidori, Lucia, Benelli, Gemma, Cinelli, Marina, Messerini, Luca, Ibba-Manneschi, Lidia, Matucci-Cerinic, Marco
Format: Article
Language:English
Subjects:
Apoptosis
Cells
Gene expression
Inflammatory bowel disease
Monoclonal antibodies
Rodents
Transgenic animals
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Summary:Rats transgenic for HLA-B27 and human β2microglobulin (B27TR) develop a multi-systemic disease resembling inflammatory bowel disease (IBD) and spondyloarthritis. TNFα has a crucial role in chronic inflammation. Our objective was to evaluate the effect of anti-TNFα treatment on spontaneous IBD in B27TR. Nine-week-old B27TR received monoclonal anti-TNFα or an isotypic IgG2a,k up to age of 18 weeks. A second group was monitored up to 18 weeks and then randomly assigned to anti-TNFα or IgG2 a,k treatment. Each rat was monitored for clinical IBD manifestations. After sacrifice, the colon was examined for pathological changes. TNFα receptors (TNF-R1, TNF-R2), Fas/Fas-L expression and apoptosis were evaluated. IgG2a,k-treated and untreated B27TR presented signs of IBD at 11 weeks, whereas in anti-TNFα-treated B27TR no IBD signs were detected. In the late treatment, IBD signs improved after 1 week. Histopathological analysis of IgG2a,k-treated B27TR colon showed inflammatory signs that were widely prevented by early anti-TNFα treatment. Late treatment did not significantly reduce inflammation. TNF-R1 was weakly expressed in intestinal epithelial cells of IgG2a,k-treated B27TR, while it was comparable to controls in anti-TNFα-treated animals. TNF-R2 immunopositivity was strongly evident in IgG2a,k-treated B27TR, whereas was absent in anti-TNFα-treated rats. RT-PCR confirmed these results. IgG2a,k-treated B27TR showed, at 18 weeks, few Fas-positive cells and an increase of Fas-L-positive cells. At 27 weeks, Fas-/Fas-L-positive cell number was significantly low. Anti-TNFα treatment increased Fas-L expression, whereas Fas increased only with the early treatment. TNFα blockade is effective in preventing inflammation in early phase of IBD, maintaining the homeostatic balance of apoptosis. [PUBLICATION ABSTRACT]
ISSN:1582-1838