¹Discipline of Pathology, Bosch Institute, School of Medical Sciences, University of Sydney, Sydney, New South Wales, Australia

Correspondence: Dr S Bao, Discipline of Pathology, University of Sydney, Room 572, Blackburn Building D06, Sydney, New South Wales 2006, Australia. E-mail: bobbao@med.usyd.edu.au

Received 2 February 2007; Revised 11 July 2007; Accepted 16 July 2007; Published online 4 September 2007.

Abstract

Tumour necrosis factor (TNF) is important in the development of inflammatory bowel disease. TNF--deficient mice show more severe colonic inflammation than wild-type (Wt) mice, but the underlying mechanism remains unclear. Using immunohistochemistry, enzyme-linked-immunosorbent assay and histopathology, we found that there was a higher level of macrophage infiltration in TNF-^-/- compared to Wt mice. This is consistent with higher levels of monocyte chemotactic protein-1, interleukin (IL)-6 and granulocyte monocyte colony-stimulating factor (GM-CSF) in the inflamed colon from the TNF-^-/- mice, compared to the Wt mice, following dextran sulphate sodium (DSS) challenge. There was close correlation between clinical observations and histopathological findings in both Wt and TNF-^-/- mice. The expression of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) was upregulated in the colon of Wt and TNF-^-/- mice following DSS challenge. Interestingly, the induction of MAdCAM-1 was relatively lower in the inflamed colon of TNF-^-/- mice, despite the higher inflammatory cell infiltrate, compared to their Wt counterparts. On the other hand, TNF-^-/- mice had significantly lower baseline levels of colonic IL-4, IL-6 and GM-CSF. Furthermore, there was a reduction of both immunoglobulin A (IgA) and IgG in the gut from TNF-^-/- mice following DSS challenge. These data indicate that TNF- deficiency alters homoeostasis of the colonic chemokine/cytokine environment and humoral immune response, resulting in an exacerbation of acute DSS-induced colitis in TNF-^-/- mice. These findings support the idea that TNF- plays a role in the acute stage of intestinal inflammation.