Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Review Blood Purif 2008;26:291–299 DOI: 10.1159/000126926 Cytokine Dysregulation in Chronic Kidney Disease: How Can We Treat It? Juan Jesus Carrero Mahmut Ilker Yilmaz Bengt Lindholm Peter Stenvinkel Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden liferation and activity of immune cells. As the kidney is the major site for elimination of many of these cytokines, the delicate equilibrium of pro-inflammatory cytokines and their inhibitors is clearly dysregulated in chronic kidney disease (CKD) patients [1, 2]. The dialysis proce- dure [3] further stimulates circulating nuclear cells for cytokine production [4], making them respond more vig- orously to exposure to endotoxins [5]. These consequenc- es of the altered immune response in uremia lead to a state of persistent inflammation [6, 7] which is highly prevalent among CKD patients and is linked to complica- tions such as the development of protein-energy wasting (PEW) and atherosclerotic vascular disease [3, 8]. In- flammation, PEW and atherosclerosis often coexist in CKD [9], and each of these risk factors independently predicts outcome in these patients. In order to under- stand this complex orchestration, selected cytokines will be reviewed with regards to our current understanding of the uremic cytokine misbalance, as well as an updated status of current and future anti-cytokine strategies in CKD. Innate and Humoral Immune System: Keeping Homeostasis as a Principle The cytokine response to infection or injury is a well- coordinated and precisely controlled process aimed at maintaining the body homeostasis. When addressing the Key Words Chronic kidney disease  Cytokine  Inflammation  Interleukin  Mortality  Dialysis Abstract As the kidney is the major site for elimination of many cyto- kines, the delicate equilibrium of pro-inflammatory cyto- kines and their inhibitors is clearly dysregulated in chronic kidney disease (CKD) patients. The consequences of the al- tered immune response in uremia lead to a state of persis- tent inflammation which is highly prevalent among CKD pa- tients and is linked to complications such as the development of protein-energy wasting and atherosclerotic vascular dis- ease. The present review aims at reviewing this complex or- chestration of uremic cytokines beyond the well-studied in- terleukin-6 and tumor necrosis factor- . Finally, we update our current understanding on anti-inflammatory treatment strategies in CKD patients, including nutritional and lifestyle measurements, pharmacological intervention and specific anticytokine strategies targeting the dialytic procedure. Copyright © 2008 S. Karger AG, Basel Introduction In the immune system, a complex orchestration of cy- tokines and other molecules act in a paracrine, autocrine or endocrine fashion to control the differentiation, pro- Published online: April 18, 2008 J.J. Carrero Divisions of Renal Medicine and Baxter Novum K56, Karolinska Institutet, University Hospital at Huddinge SE–14186 Stockholm (Sweden) Tel. +46 8 585 82601, Fax +46 8 585 83925, E-Mail juan.jesus.carrero@ki.se © 2008 S. Karger AG, Basel 0253–5068/08/0263–0291$24.50/0 Accessible online at: www.karger.com/bpu