IGPNS Faculty Mentors
Kenneth A. Kudsk, M.D.
H4736 Clinical Science Center
600 Highland Avenue
Madison WI 53792
Principal Research Interest:
The effect route and type of nutrition and malnutrition on host defenses, mucosal immunity, and vascular inflammatory responses.
The program is designed to integrate and translate laboratory discoveries into clinical testing and medical practice. The goal is to define the mechanisms related to impaired nutritional status that increase postoperative infectious and healing complications in patients who are severely injured, critically ill, or undergoing major elective surgical procedures.
The laboratory research focuses on differences in host defenses between enterally and parenterally fed animals, pursuing laboratory and clinical studies that demonstrate significant immunologic benefits when nutrients are delivered enterally compared to intravenously. After tracing many of these differences to the mucosal immune system, which constitutes 50% of the body's total immunity, our work shows that the size and integrity of mucosal immunity rapidly deteriorates when animals are not fed via the gastrointestinal tract. Simultaneously, established immunologic protection of mucosal surfaces against viruses and bacteria is lost. This system also loses its ability to respond to new pathogenic challenges.
Since investigating control mechanisms for this immune system, our group is demonstrating significant reductions in the molecules responsible for directing naïve immunocytes into and through the mucosal immune system for distribution throughout the body. The expression of these controlling molecules are related to alterations in tissue and cellular cytokine levels necessary to maintain integrity. In addition, these cytokine changes simultaneously influence changes in the vascular endothelium of the gastrointestinal tract. These changes prime neutrophils and augment deleterious inflammatory responses throughout the body to subsequent stresses. Since many patients require intravenous feeding to avoid progressive starvation, we have found that several substances, when administered exogenously, can reverse the defect in mucosal immunity associated with parenteral feeding. Specific nutrients such as glutamine or products of the enteric nervous system (neuropeptides) reverse many of the deleterious affects of IV feeding. Clinical studies with these molecules are currently being planned.
The effects of malnutrition on postoperative outcome after major general surgical procedures continue to be addressed in clinical studies. Our future work will identify specific preoperative nutritional markers predictive of a high complication rate to allow study of the effect of preoperative nutrient manipulation on improving clinical outcome by reducing postoperative complications. Collaboration with the basic science community in Nutritional Sciences and throughout UW will be an integral part of this approach.
Pierre JF, Heneghan AF, Wang X, Roennegurg DA, Groblewski GE, Kudsk KA. Bombesin Improves Adaptive Immunity of the Salivary Gland during Parenteral Nutrition. JPEN J Parenter.Enteral Nutr. 2013 Oct 11. [Epub ahead of print] PMID: 24121183
HeneghanAF , Pierre JF, Tandee K, Shanmuganayagam D, Wang X, Reed JD, Steele JL, Kudsk KA. Parenteral Nutrition Decreases Panenth cell function and Intestinal Bactericidal Activity while Increasing Susceptibility to Bacterial Enteroinvasion. JPEN J Parenter.Enteral Nutr. 2013 Jul 26. [Epub ahead of print] PMID: 23894173
Pierre JF, Heneghan AF, Meudt M, Shea MP, Krueger CG,Reed J, Kudsk KA, Shanmuganayagam D. Parenteral nutrition increases susceptibility of ileum to invasion by E. coli. J Surg Res. 2013 Aug;183(2):583-91 [2013 Feb 24. Epub ahead of print] PMID: 23481564
Heneghan AF, Pierre JF, Kudsk KA. IL-25 Improves IgA Levels During Parenteral Nutrition Through the JAK-STAT Pathway. Ann Surg. 2013 Dec; 258(6):1065-71, [Epub ahead of print] PMID:23160152 2012 Nov 15.
Heneghan AF, Pierre JF, Gosain A, Kudsk KA. IL‑25 improves luminal innate immunity and barrier function during parenteral nutrition. Ann Surg. 2014 Feb;259(2):394-400, 2013 Feb 19. [Epub ahead of print]
Kudsk KA, Hermsen JL, Genton L, Faucher L, Gomez FE. Injury stimulates an innate respiratory IgA immune response in humans. J Trauma 2008;64(2)316-325
Hermsen JL, Sano Y, Gomez FE, Maeshima Y, Kang K, Kudsk KA. Parenteral Nutrition Inhibits a Tumor Necrosis Factor-α Mediated IgA Response to Injury. Surgical Infections (Larchmt.) 2008; 9:(1) 33-40.
Kudsk KA. 2008 Rhoads Lecture: Of mice and men…..and a few hundred rats. J Parenter.Enteral Nutr. 2008;32(4):460-473. NIHMSID #60114 PubMed # 18596320
Sano Y, Gomez, FE,. Hermsen, JL, Kang W, Lan J, Maeshima Y, Kudsk KA. Parenteral nutrition induces organ specific alterations in polymeric immunoglobulin receptor levels Journal of Surgical Research 2008;149(2):236-42. NIHMSID # 70312 PubMed # 18599079
Jonker MA, Hermsen JL, Sano Y, Heneghan AF, Kudsk KA. Small Intestine Mucosal Immune System Response to Injury and the Impact of Parenteral Nutrition. (Surgery Epub 2010 December 9) NIHMSID #258649 PubMed#21145571