Interleukin-6 and interferon-?? gene polymorphisms in the development of bronchiolitis obliterans syndrome after lung transplantation1

Lu, Kim C.; Jaramillo, Andrés; Lecha, Rachel L.; Schuessler, Richard B.; Aloush, Aviva; Trulock, Elbert P.; Mendeloff, Eric N.; Huddleston, Charles B.; Patterson, G. Alexander; Mohanakumar, Thalachallour

doi:10.1097/00007890-200211150-00017

Cited by 70 publications

(43 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For the IL-6 gene, the G allele in the promoter À174 G/C is associated with high production and earlier development of BOS in lung transplant recipients. 58 We have observed that the frequency of acute persistent lung allograft rejection was increased in patients having IL-10 GCC/ACC haplotype (intermediate phenotype) associated with IL-6 G/C haplotype. 33 In contrast to the lung transplant patients, kidney transplants with the G allele are associated with long-term allograft survival.…”

Section: Interleukinmentioning

confidence: 90%

“…46,72,73 However, IFN-g may play a role in driving the chronic rejection process which would explain the association observed between IFN-g genotype and the development of OB in adult lung transplant recipients. 58,74 Lung transplant recipients who are of the high producer IFN-g genotype may be less likely to develop posttransplant lymphoproliferative disorder (PTLD). 75 Since PTLD has a viral etiology, this finding may relate to the anti-viral function of IFN-g.…”

Section: Interleukinmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacogenomics and lung transplantation: clinical implications

2006

View full text Add to dashboard Cite

Section: Interleukinmentioning

confidence: 90%

Section: Interleukinmentioning

confidence: 99%

Pharmacogenomics and lung transplantation: clinical implications

2006

View full text Add to dashboard Cite

“…In a rat model for chronic pancreatitis IL-6 tissue expression was able to be established (11). IL-6 gene polymorphism led to an increased number of chronic fibrotic lung diseases in transplanted patients (26). In addition, patients with peritoneal dialysis related chronic peritonitis exhibited increased levels of IL-6 in the peritoneal dialysate effluent (15).…”

Section: Oral Submucosis Fibrosis -(S) +(S) +(S)mentioning

confidence: 99%

Significant alterations of serum cytokine levels in patients with Peyronie's disease

et al. 2008

View full text Add to dashboard Cite

Objective: To determine the expression of the cytokines transforming growth factor-β1 (TGF-β1), interferon-γ (IFN-γ), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum from patients with Peyronie's disease (PD) compared to healthy controls. Materials and Methods: Ninety-one consecutive PD patients aged 20 -74 years were included in this study. All patients were diagnosed with symptomatic PD for the first time and had a palpable penile plaque. The patients previously had the disease for 6 -72 months. None of the patients had a severe infectious disease or known systemic illness. For cytokine analyses, peripheral venous blood samples were obtained before treatment. Fifty healthy male blood donors aged 22 -64 years served as the control group. TGF-β1, IFN-γ, Il-6, and TNF-α were analyzed quantitatively with commercial immunoassays. Results: Mean cytokine levels in serum from patients were increased for TGF-β1 and IFN-γ compared to healthy controls. The difference for TGF-β1 was considered statistically significant (p < 0.001). IL-6 was not detectable in PD patients (p < 0.01) and TNF-α was decreased (p < 0.0001). Conclusion:The significantly elevated serum level of the profibrotic TGF-β1 cytokine underscores the effect of cytokines in the pathophysiology of PD. The significantly decreased TNF-α serum level suggested no acute immunomodulatory process. Therefore, the relevance for therapeutic administration of TNF-α should be further investigated. Quantification of TGF-β1 in serum of PD patients provides a possible diagnostic tool and target for therapy. The data on altered cytokine levels in PD patients also provide a new understanding for etiopathogenesis of PD, which warrants further investigation.

show abstract

“…Similarly, polymorphisms in IL-6 and IFN-g genes that regulate the production of these cytokines have been shown to correlate with the development of BOS after lung transplantation, consistent with a proinflammatory role for IL-6 in the pathogenesis of this disease. 77 The role of these genes in both early and late pulmonary complications of HSCT setting should be evaluated. Polymorphisms that increase the risk of cGVHD might also be expected to increase the incidence of BOS.…”

Section: Future Directionsmentioning

confidence: 99%

Genomic screening and complications of hematopoietic stem cell transplantation: has the time come?

Kallianpur

2004

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:The occurrence of toxic complications following hematopoietic stem cell transplantation (HSCT) is highly variable and dependent on a multitude of host, donor, and treatment factors. The increasingly broad indications for HSCT and the need to provide this treatment option to older and/or more debilitated patients emphasizes the importance of refining our methods of predicting and ameliorating these toxicities. Late complications (occurring after day 100) also pose a threat to quality of life after HSCT. Genetic polymorphisms in key molecular pathways in the host are likely to contribute significantly to the observed variability in the development HSCT-associated complications. Hepatic veno-occlusive disease and acute lung injury, two of the most serious organ toxicities that occur, represent useful paradigms for the identification of genetic polymorphisms in enzyme systems that modulate local and systemic responses to oxidant stress during transplant conditioning therapy. Ongoing studies in this area are providing clues to the prevention of adverse clinical outcomes based on the genetic milieu. This review of studies in HSCT that explore genetic risk factors for transplant complications indicates that significant progress is being made in this rapidly evolving area. However, further large-scale clinical and translational studies are needed before genomic screening can be widely used to individualize treatment. Bone Marrow Transplantation (2005) Clinicians are continually challenged by the need to predict the responses of individual patients to potentially toxic treatments. The increasing promise of cure for patients who undergo hematopoietic stem cell transplantation (HSCT) for life-threatening disorders is overshadowed by the very real threat of short-term, often fatal, complications resulting from the transplant regimen and graft-versushost disease (GVHD). However, significant variation is observed between similarly treated individuals in the development of complications. It is an appealing concept, therefore, and one to which many clinicians now subscribe, that a significant portion of this variability has a genetic basis. Identifying important genetic variables will allow for better prediction of HSCT-related outcomes, and in the process of identifying these susceptibilities, it may also be possible to gain sufficient knowledge of the underlying pathophysiology of these toxicities to develop targeted interventions.This review will focus on genomic screening of the host for the prediction of specific complications, touching briefly on selected donor factors. Other rapidly evolving areas that are not covered include molecular genetic testing to predict graft failure and disease relapse after HSCT. The role of clinical and biochemical risk factors in the pre-transplant evaluation of HSCT candidates has also been reviewed recently in this journal. 1 Importance of context-dependent genetic effectsThe study of uncommon disease-associated mutations has been invaluable to our understanding of basic pathophy...

show abstract

Interleukin-6 and interferon-?? gene polymorphisms in the development of bronchiolitis obliterans syndrome after lung transplantation1

Abstract: The presence of high-expression polymorphisms at position -174 of the IL-6 gene and position +874 of the IFN-gamma gene significantly increases the risk for BOS development after lung transplantation.

Cited by 70 publications

References 52 publications

Pharmacogenomics and lung transplantation: clinical implications

Pharmacogenomics and lung transplantation: clinical implications

Significant alterations of serum cytokine levels in patients with Peyronie's disease

Genomic screening and complications of hematopoietic stem cell transplantation: has the time come?

Contact Info

Product

Resources

About