Interferon lambdas: the next cytokine storm

[Guest guest]

http://gut.bmj.com/content/early/2011/02/08/gut.2010.222976.short?q=w_gut_educat\

ion

Gut doi:10.1136/gut.2010.222976

Recent advances in basic science

Interferon lambdas: the next cytokine storm

Christabel ,

Klenerman,

Eleanor

+ Author Affiliations

Medawar Building for Pathogen Research and Oxford NIHR Biomedical Research

Centre, Nuffield Department of Medicine, University of Oxford, Oxford, UK

Correspondence to Dr Eleanor , Medawar Building for Pathogen

Research, Oxford NIHR Biomedical Research Centre, Nuffield Department of

Medicine, University of Oxford, South Parks Road, Oxford OX1 3SY, UK;

ellie.barnes@...

Abstract

For two decades the scientific community has sought to understand why some

people clear hepatitis C virus (HCV) and others do not. Recently, several large

genome-wide association studies have identified single nucleotide polymorphisms

(SNPs) linked to interferon lambda 3 (IFNë3) that are associated with the

spontaneous resolution and successful treatment of HCV infection. These

observations are generating intense research activity; the hope is that IFNë3

genetic variants may serve as important predictive biomarkers of treatment

outcome and offer new insights into the biological pathways involved in viral

control. A pharmacogenomic treatment approach for HCV can now be envisaged, with

the incorporation of host genetic variants into a predictive treatment algorithm

with other factors. The SNPs associated with the clinical outcome of HCV

infection are located some distance from the IFNë3 gene itself, and causal

genetic variants have yet to be clearly defined. Locating these causal variants,

mapping in detail the IFNë3 signalling pathways and determining the downstream

genetic signature so induced will clarify the role of IFNë3 in the pathogenesis

of HCV. Clinical studies assessing safety and efficacy in the treatment of HCV

with exogenous IFNë3 are currently underway. Early results suggest that IFNë3

treatment inhibits HCV replication and is associated with a limited side effect

profile. However, hepatotoxicity in both healthy volunteers and HCV-infected

patients has been described. This review discusses the genetic studies that link

IFNë3 to both the spontaneous resolution and treatment-induced clearance of HCV

and the potential impact of this in clinical practice, the biology of IFNë3 as

currently understood and how this may impact on HCV infection, and describes the

early studies that assess the role of this cytokine in the treatment of patients

with HCV.

[Guest guest]

http://gut.bmj.com/content/early/2011/02/08/gut.2010.222976.short?q=w_gut_educat\

ion

Gut doi:10.1136/gut.2010.222976

Recent advances in basic science

Interferon lambdas: the next cytokine storm

Christabel ,

Klenerman,

Eleanor

+ Author Affiliations

Medawar Building for Pathogen Research and Oxford NIHR Biomedical Research

Centre, Nuffield Department of Medicine, University of Oxford, Oxford, UK

Correspondence to Dr Eleanor , Medawar Building for Pathogen

Research, Oxford NIHR Biomedical Research Centre, Nuffield Department of

Medicine, University of Oxford, South Parks Road, Oxford OX1 3SY, UK;

ellie.barnes@...

Abstract

For two decades the scientific community has sought to understand why some

people clear hepatitis C virus (HCV) and others do not. Recently, several large

genome-wide association studies have identified single nucleotide polymorphisms

(SNPs) linked to interferon lambda 3 (IFNë3) that are associated with the

spontaneous resolution and successful treatment of HCV infection. These

observations are generating intense research activity; the hope is that IFNë3

genetic variants may serve as important predictive biomarkers of treatment

outcome and offer new insights into the biological pathways involved in viral

control. A pharmacogenomic treatment approach for HCV can now be envisaged, with

the incorporation of host genetic variants into a predictive treatment algorithm

with other factors. The SNPs associated with the clinical outcome of HCV

infection are located some distance from the IFNë3 gene itself, and causal

genetic variants have yet to be clearly defined. Locating these causal variants,

mapping in detail the IFNë3 signalling pathways and determining the downstream

genetic signature so induced will clarify the role of IFNë3 in the pathogenesis

of HCV. Clinical studies assessing safety and efficacy in the treatment of HCV

with exogenous IFNë3 are currently underway. Early results suggest that IFNë3

treatment inhibits HCV replication and is associated with a limited side effect

profile. However, hepatotoxicity in both healthy volunteers and HCV-infected

patients has been described. This review discusses the genetic studies that link

IFNë3 to both the spontaneous resolution and treatment-induced clearance of HCV

and the potential impact of this in clinical practice, the biology of IFNë3 as

currently understood and how this may impact on HCV infection, and describes the

early studies that assess the role of this cytokine in the treatment of patients

with HCV.