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Am J Physiol Gastrointest Liver Physiol 276: G1461-G1472, 1999;
0193-1857/99 $5.00
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Vol. 276, Issue 6, G1461-G1472, June 1999

IL-2-deficient mice raised under germfree conditions develop delayed mild focal intestinal inflammation

Michael Schultz1, Susan L. Tonkonogy2, Rance K. Sellon2, Claudia Veltkamp1, Virginia L. Godfrey3, Julie Kwon2, Wetonia B. Grenther2, Edward Balish4, Ivan Horak5, and R. Balfour Sartor1

1 Center for Gastrointestinal Biology and Disease, Department of Medicine, and 3 Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill 27599; and 2 College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606; 4 Departments of Surgery, Medical Microbiology, and Immunology, University of Wisconsin, Madison, Wisconsin 53706; and 5 Institute of Molecular Pharmacology, Department of Molecular Genetics, 12207 Berlin, Germany

Interleukin-2 (IL-2) amplifies immune stimuli and influences B cell differentiation. IL-2-deficient mice spontaneously develop intestinal inflammation if raised under specific pathogen-free (SPF) conditions. We quantitatively determined the aggressiveness and kinetics of gastrointestinal and hepatic inflammation in the presence or absence of viable bacteria in IL-2-deficient mice. Breeding colonies were maintained under SPF and germfree (GF) conditions. Intestinal tissues, serum, and mesenteric lymph nodes were obtained from mice at different ages for blind histological scoring, immunoglobulin measurements, mucosal T cell infiltration, and cytokine secretion. GF IL-2 -/- mice developed mild, focal, and nonlethal intestinal inflammation with delayed onset, whereas the more aggressive inflammation in SPF IL-2 -/- mice led to their death between 28 and 32 wk. Periportal hepatic inflammation was equal in the presence or absence of bacterial colonization. Intestinal immunoglobulin secretion decreased significantly by 13 wk of age in IL-2 -/- mice in both GF and SPF environments. In contrast to other genetically engineered rodents, IL-2 -/- mice develop mild focal gastrointestinal and active portal tract inflammation in the absence of viable bacteria.

interleukin-2-deficient mice; luminal flora; colitis; animal models


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