Low Levels of Th1-Type Cytokines and Increased Levels of Th2-Type Cytokines in Kidney Transplant Recipients With Active Cytomegalovirus Infection

Essa, Sahar; Pacsa, A.S.; Raghupathy, Raj; Said, T; Nampoory, M.R.N.; Johny, K.V.; Al‐Nakib, W.

doi:10.1016/j.transproceed.2008.10.098

Cited by 16 publications

(26 citation statements)

References 22 publications

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“…As serum levels of cytokines may variably be influenced by other CMV‐ independent factors in vivo , results on the systemic response induced in the course of CMV infection are heterogeneous. Some studies report a predominance of T‐helper (Th)2 cytokines , whereas others largely found a Th1 cytokine signature . We now assessed cytokines expressed by PBMC in response to specific stimulation with CMV antigen and related those findings to phenotypical signs of CMV‐specific T‐cell anergy, defined by PD‐1 expression.…”

Section: Discussionmentioning

confidence: 99%

Blockade of programmed death receptor‐1 signaling restores expression of mostly proinflammatory cytokines in anergic cytomegalovirus‐specific T cells

Dirks

Egli

Sester

et al. 2012

Transplant Infectious Dis

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Taken together, this pilot study provides evidence that a high PD-1 expression on CMV-specific T cells actively impairs proliferation and "cytokinome" responses in an antigen-specific manner. Importantly, blockade of PD-L restores CMV-specific T-cell proliferation and expression of a panel of different proinflammatory and/or type 1 cytokines, suggesting a common but as yet unknown regulatory principle. We conclude that PD-1 exhaustion is reversible and potentially amenable to therapeutic ex vivo and possibly in vivo manipulation. However, detailed knowledge of the differential effects on the "cytokinome" will be necessary to increase the safety and the efficacy of such manipulations.

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Section: Discussionmentioning

confidence: 99%

Blockade of programmed death receptor‐1 signaling restores expression of mostly proinflammatory cytokines in anergic cytomegalovirus‐specific T cells

Dirks

Egli

Sester

et al. 2012

Transplant Infectious Dis

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“…HCMV infection affects allograft outcomes by affecting cellular and humoral responses, including plasma cytokine production [37]. HCMV replication in renal transplant recipients is associated with increased IL-6 and decreased IFN-γ in mononuclear cell levels in plasma and peripheral blood [37,38]. HCMV DNA levels, detected by real-time PCR in whole blood, represent a precise method for determining viral load kinetics, growth suppression, cell death, tumor immunity and autoimmunity [28].…”

Section: Discussionmentioning

confidence: 99%

Cytokine Production and Human Cytomegalovirus Load in Allogeneic Hematopoietic Stem Cell Transplantation Outcome

TA¹

2016

Int J Immunother Cancer Res

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Objective: To investigate the impact of cytokine levels (IL-1β, IL-6, IL-10, IFN-γ and TNF-α) and Human cytomegalovirus (HCMV) load in the saliva and blood on the survival of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients.Study Design: Samples were obtained from 63 patients 7 days before and 21 days after allo-HSCT. Cytokine levels were assessed by ELISA, and HCMV load was determined by real-time PCR. Results:The increase of IL-6 in the saliva and the reduction of IFN-γ in the blood before allo-HSCT were associated with increased risk of death. Moreover, the increase of IL-6 in the blood and of HCMV in the saliva after allo-HSCT were also associated with increased risk of death. Conclusions:Cytokine levels and HCMV load were associated with the increased risk of death. The findings suggest a potential function of these biomarkers in the determination of allo-HSCT survival.factor-α (TNF-α) and interleukin-1 (IL-1), could be increased as a result of disease, therapy, comorbidities or ongoing infections that occur before allo-HSCT. Second, immediately after allo-HSCT, the immune dysfunction caused by the conditioning regimen, which may produce tissue injury and consequently the production of inflammatory cytokines, may affect the reconstitution of white blood cells. Third, after allo-HSCT, activated, mature donor T-cells can set off a cytokine response that in turn stimulates host T-cell responses related to the onset of acute graft-versus-host disease (aGVHD) [3,4]. Immune dysfunction following allo-HSCT involves activated T-cells secreting interferon (IFN)-γ as well as other cytokines, which activate monocytes and dendritic cells. This process appears to be associated with the induction of aGVHD, resulting in significant morbidity and mortality. In addition, a prolonged immune deficiency characterized by lymphopenia and susceptibility to infection can occur [2]. Deregulation of inflammatory cytokines is also associated with multiple symptoms (pain, sleep disturbance and depression) during neutropenia after allo-HSCT [3]. Interleukin-6 (IL-6) is an important pro-inflammatory cytokine involved in immune-mediated complications after allo-HSCT [5].Human cytomegalovirus (HCMV) infection remains one of the most important causes of morbidity and mortality among allo-HSCT recipients [6,7]. Infection by HCMV may result not only in HCMV disease, but is also associated with other adverse effects due to its immunomodulatory actions; this might result in increased risk of bacterial, fungal and viral infections, and also of aGVHD [8].Allo-HSCT outcomes could be affected by factors such as HCMV infection, recipient/donor histocompatibility, patient/donor gender,

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“…In addition, we observed that low levels of IL-1b in the blood are associated with increased risk of death after allo-HSCT. Finally, reduced levels of IFN-c were reported to be involved HCMV gB genotype and its association with cytokine levels JF Correia-Silva et al with reduced cell-mediated immunity to HCMV and development of viral infection (Essa et al, 2009). In multivariate analysis, we observed that decreased IL-1b and increased IL-10 levels in the blood decrease survival of allo-HSCT patients.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, we observed that low levels of IL‐1β in the blood are associated with increased risk of death after allo‐HSCT. Finally, reduced levels of IFN‐γ were reported to be involved with reduced cell‐mediated immunity to HCMV and development of viral infection (Essa et al , 2009).…”

Section: Discussionmentioning

confidence: 99%

“…In multivariate analysis, we observed that decreased IL‐1β and increased IL‐10 levels in the blood decrease survival of allo‐HSCT patients. Recently, an association between decreased pro‐inflammatory cytokines and increased anti‐inflammatory cytokines with reduced cell‐mediated immunity to HCMV has been demonstrated (Essa et al , 2009). Our study gives further strength to the theory that the imbalance of inflammatory response is not desirable for allo‐HSCT patients.…”

Section: Discussionmentioning

confidence: 99%

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HCMV gB genotype and its association with cytokine levels in hematopoietic stem cell transplantation

et al. 2011

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Low Levels of Th1-Type Cytokines and Increased Levels of Th2-Type Cytokines in Kidney Transplant Recipients With Active Cytomegalovirus Infection

Cited by 16 publications

References 22 publications

Blockade of programmed death receptor‐1 signaling restores expression of mostly proinflammatory cytokines in anergic cytomegalovirus‐specific T cells

Blockade of programmed death receptor‐1 signaling restores expression of mostly proinflammatory cytokines in anergic cytomegalovirus‐specific T cells

Cytokine Production and Human Cytomegalovirus Load in Allogeneic Hematopoietic Stem Cell Transplantation Outcome

HCMV gB genotype and its association with cytokine levels in hematopoietic stem cell transplantation

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