(Gut 2001;48:176-185)

No abstract

The gastrointestinal (GI) tract is exposed to a wide range of microorganisms. The expression of antimicrobial peptides has been demonstrated in different regions of the GI tract, predominantly in epithelial cells, which represent the first host cells with which the microorganisms have to interact for invasion. The intestinal epithelial monolayer is complex, consisting of different cell types, and most have a limited lifespan. Of the GI antimicrobial peptides, alpha- and beta-defensins have been studied the most and are expressed by distinct types of epithelial cells. Enteric alpha-defensin expression is normally restricted to Paneth and intermediate cells in the small intestine. However, there are important differences between mice and humans in the processing of the precursor forms of enteric alpha-defensins. Parasite infection induces an increase in the number of enteric alpha-defensin-expressing Paneth and intermediate cells in the murine small intestine. In the chronically inflamed colonic mucosa, metaplastic Paneth cells (which are absent in the normal colon) also express enteric alpha-defensins. Epithelial expression of beta-defensins may be constitutive or inducible by infectious and inflammatory stimuli. The production of some members of the beta-defensin family appears to be restricted to distinct parts of the GI tract. Recent studies using genetically manipulated rodents have demonstrated the likely in vivo importance of enteric antimicrobial peptides in innate host defense against microorganisms. The ability of these peptides to act as chemoattractants for cells of the innate- and adaptive-immune system may also play an important role in perpetuating chronic inflammation in the GI tract.

The side‐effects suitable for monitoring in patients with inflammatory bowel disease being treated with the four main groups of drugs (5‐aminosalicylic acid preparations, azathioprine and 6‐mercaptopurine, methotrexate, and corticosteroids) are reviewed. On the basis of the reported frequency, severity and timing of side‐effects, a practical scheme of monitoring is recommended. This includes a baseline measurement of full blood count, creatinine and liver function tests in all patients. In the absence of worrying symptoms, we recommend the following: (i) no monitoring for sulfasalazine; (ii) for other 5‐aminosalicylic acid preparations, the meas‐ urement of creatinine at 6 and 12 months and then annually; (iii) for azathioprine/6‐mercaptopurine, thiopurine methyltransferase genotype/phenotype determination has no role in treatment monitoring, but a full blood count at 2 weeks, 1 month, 3 months and then every 3 months should be performed; (iv) for methotrexate, a full blood count and liver function tests should be performed every 3 months; (v) for steroids, dual energy X‐ray absorptiometry bone scanning should be performed at the start of therapy, every year in which steroids are used if the T score is < 0, and every 3–5 years if the T score is > 0.

HNP 1-3 and lysozyme are expressed in surface enterocytes of mucosa with active IBD and they may play an important role in intestinal host defence against luminal microorganisms.