Dysregulated cytokine responses during cytomegalovirus infection in renal transplant recipients.
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.
Sadeghi
Mahmoud
M
Department of Transplantation Immunology, University of Heidelberg, Heidelberg, Germany. mahmoud.sadeghi@med.uni-heidelberg.de
Daniel
Volker
V
Naujokat
Cord
C
Schnitzler
Paul
P
Schmidt
Jan
J
Mehrabi
Arianeb
A
Zeier
Martin
M
Opelz
Gerhard
G
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
D016207:Cytokines; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D007371:Interferon-gamma