TH1/TH2 cytokine release pattern during in vivo cytomegalovirus disease in solid organ transplantation.
BACKGROUND
Cytomegalovirus (CMV) disease is associated with an increased net immunosuppressive state in solid organ transplant recipients, leading to more bacterial and fungal infections. The release of pro- and anti-inflammatory cytokines could be one of the responsible factors.


METHODS
We prospectively included all patients undergoing solid organ transplantation between April and November 2004. During follow-up, plasma samples were collected in the immediate postsurgical period, at the first and second months, at the time of maximum antigenemia during CMV disease, and at 6 months posttransplantation. We determine the levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10. Log-transformed data were compared by a nonparametric Wilcoxon test for related variables.


RESULTS
During the study period, we monitored 146 recipients of solid organ transplantation: 77 kidneys, 8 kidney-pancreas, 46 liver, 11 heart, 2 liver-kidney, and 2 heart-kidney. No differences were observed between the TNF-alpha and IL-10 levels in the immediate postsurgical period or during CMV disease. TNF-alpha and IL-10 levels during CMV disease were higher than levels during the first month (mean TNF-alpha first month = 12.71 pg/mL vs CMV disease = 22.71 pg/mL, P = .028; mean IL-10 first month = 3.47 pg/mL vs CMV disease = 19.2 pg/mL, P = .018). Th1/Th2 ratio (measured as TNF-alpha/IL-10) was 1.75 in the immediate postsurgical period, 7.5 during the first month, 1.86 at the time of CMV disease, and 4.61 at the sixth month. The difference in Th1/Th2 ratio during CMV disease and in the first month was statistically significant (P = .043).


CONCLUSIONS
During CMV disease, we observed an increase in TNF-alpha and IL-10 release, which was similar to that during the postsurgical period. An imbalance toward an anti-inflammatory pattern was noted in these two periods. This could reflect a cooperative factor increasing the net state of immunosuppression during CMV disease.
Cervera
C
C
Infectious Diseases Service, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain. ccervera@clinic.ub.es
Filella
X
X
Linares
L
L
Pineda
M
M
Esteva
C
C
Antón
A
A
Marcos
M A
MA
Cofán
F
F
Navasa
M
M
Pérez-Villa
F
F
Pumarola
T
T
Moreno
A
A
D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D003586:Cytomegalovirus Infections / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D005500:Follow-Up Studies; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016377:Organ Transplantation / Q000706:statistics & numerical data*; D011446:Prospective Studies; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014181:Transplantation Immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10