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Decreased Enteral Stimulation Alters Mucosal Immune Chemokines

Joshua L. Hermsen, MD^*, F. Enrique Gomez, PhD^*, Yoshinori Maeshima, MD^*, Yoshifumi Sano, MD^*, Woodae Kang, MD, PhD^* and Kenneth A. Kudsk, MD^*,

From the ^* Department of Surgery, School of Medicine and Public Health, University of Wisconsin–Madison, Madison, Wisconsin; and William S. Middleton Veterans Administration Hospital, Madison, Wisconsin

Correspondence: Kenneth A. Kudsk, MD, Department of Surgery, School of Medicine and Public Health, University of Wisconsin–Madison, H4/736 Clinical Science Center, Madison, WI 53792-7375. Electronic mail may be sent to kudsk{at}surgery.wisc.edu.

Background: Migration of lymphocytes into and through the mucosal immune system depends upon adhesion molecules to attract circulating cells and chemokines to stimulate diapedesis into tissues. Decreased enteral stimulation significantly reduces mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) levels, an adhesion molecule critical for homing of T and B cells to Peyer's patches (PP), which reduces PP and intestinal T and B cells. We studied the effect of type and route of nutrition on tissue specific chemokines in PP (CXCL-12, -13 and CCL-19, -20 and -21), small intestine (SI; CCL-20, -25 and -28) and lung (CXCL-12, CCL-28). Methods: Intravenously cannulated male Institute of Cancer Research (ICR) mice were randomized to chow or parenteral nutrition (PN) for 5 days. PP, SI, and lung chemokine mRNA levels were measured using real-time qRT–polymerase chain reaction, and analyzed semiquantitatively by the Ct method. Protein levels were quantified using enzyme-linked immunosorbent assay (ELISA) techniques, and groups compared using Student's t-test. Results: PP CXCL13 protein significantly decreased, whereas CCL21 protein increased significantly in the parenterally fed group. Parenteral feeding significantly decreased SI CCL20 and CCL 25 protein levels. CCL28 decreased significantly in the SI and lung of intravenously fed animals. mRNA levels changed in the opposite direction (compared with protein) for all chemokines except CCL28. Conclusions: Decreased enteral stimulation significantly alters key mucosal immune chemokine protein levels at multiple sites. In general, PN (and concomitant lack of enteral stimulation) results in decreased levels of chemokines that control lymphocyte migration within the mucosal immune system.

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