Introduction: Barrett's metaplasia (BM) is a chronic inflammatory disorder of the oesophagus in response to persistent gastro-oesophageal reflux and is associated with two distinct complications: benign oesophageal strictures and a 125-fold increased risk of developing an oesophageal adenocarcinoma. Benign strictures usually form in proximal areas of BM whereas adenocarcinomas arise distally. The characteristics of the inflammation and its role in the development of these complications have however been unclear.

Hypothesis: We propose that different immune responses are involved in the pathogeneses of these complications and that inflammation in BM is not a homogenous condition.

Methods: Endoscopic biopsies were obtained from normal oesophageal mucosa (n=10), oesophagitis (n=10) and paired biopsies from proximal and distal BM (n=20). The samples were assessed using immunohistochemistry, immunofluorescence, western blotting, and PCR amplification of DNA isolates from paraffin-embedded biopsies with consensus primers TCRB, TCRG and IgH.

Results: We have shown that two distinct areas exist within BM based on cytokine production and inflammatory cell phenotype. Proximal segments of BM were associated with more intense inflammation and a polyclonal population of CD4 lymphocytes, CD8 lymphocytes and macrophages (CD68). Distal segments of BM were however significantly less inflamed and were characterised by a predominance of monoclonal CD4 lymphocytes. Proximal segments were associated with increased production of interferon γ, interleukin 1β, interleukin 2 and interleukin 12 suggesting a TH1-type immune response whereas distal segments were associated with production of interleukin 4, interleukin 5 and interleukin 10 suggesting a TH2-type immune response. In both areas the majority of inflammatory cells were located around the bases of the crypts and deep glands with significantly fewer cells at the luminal surface.

Conclusions: Our data suggest that BM is not a homogenous condition but that benign stricture and adenocarcinoma formation are associated with distinct immune responses and different pathogeneses.