GUT 1997;41:793-800 ( December )

Cytokine mRNA expression in intestinal tissue of interleukin-2 deficient mice with bowel inflammation

I B Autenrieth,^a N Bucheler,^a E Bohn,^a G Heinze,^a I Horak^b

^a Max v. Pettenkofer Institut für Hygiene und Medizinische Mikrobiologie, Ludwig Maximilians Universität, Pettenkoferstrasse 9a, D-80336 München, Germany, ^b Institute for Virology and Immunobiology, University of Wurzburg, Wurzburg, Germany

Correspondence to: Dr Autenrieth.

Accepted for publication 28 January 1997

BackgroundMice deficient in interleukin-2 (IL-2) develop inflammatory bowel disease resembling ulcerative colitis in humans. Recent studies provided evidence that T cells, particularly CD4 T cells, rather than B cells, are involved in the pathogenesis of bowel inflammation of IL-2 deficient mice.
AimTo analyse the pattern of expression of cytokine mRNA in intestinal tissue of normal and IL-2 deficient mice.
MethodsExpression of -actin, IL-1, IL-1, IL-6, IL-10, tumour necrosis factor  (TNF-), interferon  (IFN-) and transforming growth factor 1 (TGF-1) mRNA was analysed in colon and small intestinal tissue of both IL-2 deficient (IL-2/) mice and normal (wild type) litter mates (IL-2+/+) at different ages by using qualitative, as well as semiquantitative, competitive reverse transcription polymerase chain reaction (RT-PCR). Results were correlated with the phase of progression of the disease, as determined by histology.
ResultsIL-2/ mice had expressed low levels of IL-1, IL-1, IL-6, TNF-, and IFN- mRNA in the colon by 1.5 weeks of age. In advance of the development of histologically and clinically detectable bowel inflammation, expression of IL-1, IL-1, IL-6, TNF-, IFN-, and IL-10, but not TGF-1, mRNA increased in the colon of IL-2 deficient mice. In contrast, IL-2+/+ mice expressed TGF-1 mRNA in colon tissue at 13 and 23 weeks of age, but not IL-1, IL-1, IL-6, TNF-, IL-10, or IFN- mRNA. Levels of expression of cytokine mRNA in tissue from the small intestine were comparable in IL-2/ and IL-2+/+ mice.
ConclusionsBowel inflammation in IL-2 deficient mice is preceded by an increase in IL-1, IL-1, TNF-, and IFN- mRNA expression in colon tissue. Low levels of TGF-1, but high levels of IL-1, IL-1, IL-6, TNF-, IFN-, and IL-10 mRNA expression correlate with the manifestation of severe colitis, and suggest that T cells and macrophages are involved in bowel inflammation of IL-2 deficient mice.
(GUT 1997;41:793-800)

Keywords: cytokine;  mRNA expression;  interleukin-2 deficient mice;  bowel inflammation

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© 1997 by Gut
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