Abstract
BackgroundCytomegalovirus seropositivity is an independent risk factor for atherosclerosis in patients with ESRD. Donor CMV seropositivity is associated with higher graft loss. Dendritic cells, macrophages and Th17 lymphocytes are defined as producers of IL-23. IL-23 is thought to be involved in the promotion of Th17 cell polarization. Latent CMV-induced Th17 might be involved in the pathogenesis of CMV infection in patients with ESRD. We aimed to evaluate associations of Th17-dependent cytokines with ESRD, CMV status and post-transplant outcome in kidney transplantation.ResultsIL-21 plasma levels were similar in patients and healthy controls (p = 0.47), whereas IL-9 (p = 0.02) and IL-23 (p < 0.0001) levels were significantly higher in ESRD patients. CMV-seronegative (p = 0.002) and –seropositive (p < 0.001) patients had significantly higher IL-23 plasma levels than controls. CMV-seropositive patients showed excessively higher IL-23 (p < 0.001) plasma levels than CMV-seronegative patients. Patients with post-transplant CMV reactivation had higher IL-23 plasma levels than patients without CMV reactivation (p = 0.025).ConclusionsOur results indicate that latent CMV induces IL-23. IL-23 might be an inflammatory mediator of latent CMV infection in patients with ESRD and predisposes patients for post-transplant CMV reactivation.
Highlights
Cytomegalovirus seropositivity is an independent risk factor for atherosclerosis in patients with End-stage renal diseases (ESRD)
There was a trend of higher IL-9 plasma levels in CMV-seropositive compared with CMV-seronegative patients (p = 0.02) whereas IL-21 was similar in both patient groups (p = 0.12) (Table 1)
Sixteen of 25 CMV-Immunoglobulin G (IgG)- and 9 of 28 CMV-IgG+ patients had undetectable IL-17 (p = 0.02) and CMV-IgG+ patients showed a trend of higher IL-17 plasma levels than patients without CMV-IgG (7.5 ± 7.4 pg/ml vs 5.2 ± 10.0: p = 0.06) suggesting that Th17 cells were activated (Fig. 3)
Summary
Cytomegalovirus seropositivity is an independent risk factor for atherosclerosis in patients with ESRD. Macrophages and Th17 lymphocytes are defined as producers of IL-23. Latent CMV-induced Th17 might be involved in the pathogenesis of CMV infection in patients with ESRD. We aimed to evaluate associations of Th17-dependent cytokines with ESRD, CMV status and post-transplant outcome in kidney transplantation. End-stage renal diseases (ESRD) are associated with immunodeficiency and inflammation [1]. The cytokine IL-23 is produced by dendritic cells, macrophages, and Th17 pro-inflammatory cells [4, 5]. IL-23 is thought to be involved in the promotion of Th17 cell polarization. Th17 cells produce IL-17 and IL-22 and play an essential role in inflammatory diseases [5, 6].
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