title: Dysregulated cytokine responses during cytomegalovirus infection in renal transplant recipients.
abstract: OBJECTIVE
  Pre- and posttransplant predisposing factors for cytomegalovirus (CMV) activation and disease are not well defined. The aim of this study was to examine whether there are differences in plasma cytokine levels pretransplant, before and during CMV replication in renal transplant recipients.
  
  
  METHODS
  We studied 76 renal transplant recipients in whom CMV-DNA was studied at regular intervals posttransplant. Thirty-eight patients developed CMV viremia posttransplant (CMV-DNA-positive). Thirty-eight patients had no detectable CMV-DNA posttransplant (CMV-DNA-negative). Cytokine and cytokine receptors/antagonists plasma levels were measured pretransplant, and pre-, during, and after CMV-viremia in CMV-DNA-positive patients and at similar time points in CMV-DNA-negative transplant recipients.
  
  
  RESULTS
  Compared with pretransplant, after transplantation soluble (s) plasma interleukin (IL)-2 receptor (R), IL-6, and interferon-gamma (IFN-gamma) decreased in both groups (CMV-DNA-positive: P=0.002; P=0.028; P=0.032; CMV-DNA-negative: P=0.001; P=0.040; P=0.030) whereas IL-10 remained constant in both groups (P=n.s.). During CMV viremia, sIL-2R (P=0.015) and IL-6 (P=0.006) increased compared with previremia but remained constant in CMV-DNA-negative patients matched for the day of investigation (P=n.s.). Simultaneously, IFN-gamma increased in CMV-DNA-negative patients (P=0.008) and remained constant in CMV-DNA-positive patients (P=n.s.). During CMV viremia, IL-10 (P=0.002) and sIL-2R (P=0.007) were significantly higher in CMV-DNA-positive than CMV-DNA-negative patients investigated at similar time points.
  
  
  CONCLUSIONS
  Our results indicate that CMV replication in renal transplant recipients is associated with increased sIL-2R, IL-6, and IL-10 and decreased IFN-gamma plasma levels, pointing to a monocyte/Th2 activation and a Th1 blockade. The high IL-10 might decrease the IFN-gamma plasma levels in CMV-DNA-positive patients. Th1 deficiency in CMV-DNA-positive patients might promote development of CMV disease.
authors.affiliation: Department of Transplantation Immunology, University of Heidelberg, Heidelberg, Germany. mahmoud.sadeghi@med.uni-heidelberg.de
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Sadeghi
authors.forename: Volker
authors.initials: V
authors.lastname: Daniel
authors.forename: Cord
authors.initials: C
authors.lastname: Naujokat
authors.forename: Paul
authors.initials: P
authors.lastname: Schnitzler
authors.forename: Jan
authors.initials: J
authors.lastname: Schmidt
authors.forename: Arianeb
authors.initials: A
authors.lastname: Mehrabi
authors.forename: Martin
authors.initials: M
authors.lastname: Zeier
authors.forename: Gerhard
authors.initials: G
authors.lastname: Opelz
mesh_terms: D000328:Adult; D016207:Cytokines / Q000378:metabolism*; D003587:Cytomegalovirus / Q000378:metabolism*; D003586:Cytomegalovirus Infections / Q000150:complications / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000150:complications / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D007371:Interferon-gamma