Abstract:

The discovery and initial description of the interferon-lambda (IFN-lambda) family in early 2003 opened an exciting new chapter in the field of IFN research. There are 3 IFN-lambda genes that encode 3 distinct but highly related proteins denoted IFN-lambda1, -lambda2, and -lambda3. These proteins are also known as interleukin-29 (IL-29), IL-28A, and IL-28B, respectively. Collectively, these 3 cytokines comprise the type III subset of IFNs. They are distinct from both type I and type II IFNs for a number of reasons, including the fact that they signal through a heterodimeric receptor complex that is different from the receptors used by type I or type II IFNs. Although type I IFNs (IFN-alpha/beta) and type III IFNs (IFN-lambda) signal via distinct receptor complexes, they activate the same intracellular signaling pathway and many of the same biological activities, including antiviral activity, in a wide variety of target cells. Consistent with their antiviral activity, expression of the IFN-lambda genes and their corresponding proteins is inducible by infection with many types of viruses. Therefore, expression of the type III IFNs (IFN-lambdas) and their primary biological activity are very similar to the type I IFNs. However, unlike IFN-alpha receptors which are broadly expressed on most cell types, including leukocytes, IFN-lambda receptors are largely restricted to cells of epithelial origin. The potential clinical importance of IFN-lambda as a novel antiviral therapeutic agent is already apparent. In addition, preclinical studies by several groups indicate that IFN-lambda may also be useful as a potential therapeutic agent for other clinical indications, including certain types of cancer.

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Interferon-Lambda: A New Addition to an Old Family

Raymond Donnelly

Sergei Kotenko

^{Division of Therapeutic Proteins, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland.}

^{Department of Biochemistry and Molecular Biology, University Hospital Cancer Center, University of Medicine and Dentistry of New Jersey (UMDNJ), Newark, New Jersey.}

^{Corresponding author.}

Address correspondence to: Dr. Raymond P. Donnelly, Division of Therapeutic Proteins, Center for Drug Evaluation and Research, Food and Drug Administration, Building 29A, Room 3B15, 29 Lincoln Drive, Bethesda, MD 20892. E-mail:vog.shh.adf@yllennod.dnomyar

Dr. Sergei Kotenko, Department of Biochemistry and Molecular Biology, University Hospital Cancer Center, University of Medicine and Dentistry of New Jersey (UMDNJ), 185 South Orange Av., Newark, NJ 07103. E-mail:Email: ude.jndmu@esknetok

Address correspondence to: Dr. Raymond P. Donnelly, Division of Therapeutic Proteins, Center for Drug Evaluation and Research, Food and Drug Administration, Building 29A, Room 3B15, 29 Lincoln Drive, Bethesda, MD 20892. E-mail:vog.shh.adf@yllennod.dnomyarDr. Sergei Kotenko, Department of Biochemistry and Molecular Biology, University Hospital Cancer Center, University of Medicine and Dentistry of New Jersey (UMDNJ), 185 South Orange Av., Newark, NJ 07103. E-mail:Email: ude.jndmu@esknetok

Received 2010 Jul 7; Accepted 2010 Jul 7.

Abstract

The discovery and initial description of the interferon-λ (IFN-λ) family in early 2003 opened an exciting new chapter in the field of IFN research. There are 3 IFN-λ genes that encode 3 distinct but highly related proteins denoted IFN-λ1, -λ2, and -λ3. These proteins are also known as interleukin-29 (IL-29), IL-28A, and IL-28B, respectively. Collectively, these 3 cytokines comprise the type III subset of IFNs. They are distinct from both type I and type II IFNs for a number of reasons, including the fact that they signal through a heterodimeric receptor complex that is different from the receptors used by type I or type II IFNs. Although type I IFNs (IFN-α/β) and type III IFNs (IFN-λ) signal via distinct receptor complexes, they activate the same intracellular signaling pathway and many of the same biological activities, including antiviral activity, in a wide variety of target cells. Consistent with their antiviral activity, expression of the IFN-λ genes and their corresponding proteins is inducible by infection with many types of viruses. Therefore, expression of the type III IFNs (IFN-λs) and their primary biological activity are very similar to the type I IFNs. However, unlike IFN-α receptors which are broadly expressed on most cell types, including leukocytes, IFN-λ receptors are largely restricted to cells of epithelial origin. The potential clinical importance of IFN-λ as a novel antiviral therapeutic agent is already apparent. In addition, preclinical studies by several groups indicate that IFN-λ may also be useful as a potential therapeutic agent for other clinical indications, including certain types of cancer.

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