IL-6 and NF-IL6 in Acute-Phase Response and Viral Infection

Immunol Rev. 1992 Jun;127:25-50. doi: 10.1111/j.1600-065x.1992.tb01407.x.

Abstract

NF-IL6 was originally identified as a DNA-binding protein responsible for IL-1-stimulated IL-6 induction. Direct cloning of NF-IL6 revealed its homology with C/EBP. C/EBP is expressed in liver and adipose tissues and is supposed to regulate several hepatocyte- and adipocyte-specific genes. In contrast, NF-IL6 is suppressed in normal tissues, but is rapidly and drastically induced by LPS or inflammatory cytokines such as IL-1, TNF, and IL-6. NF-IL6 can also bind to the regulatory region of various genes including IL-8, G-CSF, IL-1 and immunoglobulin genes. Furthermore, NF-IL6 is shown to be identical to IL-6DBP, a DNA-binding protein responsible for IL-6-mediated induction in acute-phase proteins, demonstrating that NF-IL6 is responsible for the genes regulated by IL-6. These results indicate that NF-IL6 may be a pleiotropic mediator of many inducible genes involved in acute, immune, and inflammatory responses, like NFkB. In this regard, it is noteworthy that both an NF-IL6 binding site and an NFkB binding site are present in the inducible genes such as IL-6, IL-8, and several acute-phase genes. On the other hand, accumulating evidence has revealed that overproduction of IL-6 may be responsible for the pathogenesis and/or several symptoms of a variety of diseases, including autoimmune diseases, malignancies, and viral diseases. At present, the molecular mechanisms of abnormal expression of the IL-6 gene are not known. Recently it has become evident that interplays between viral proteins and cellular proteins play an important role in viral oncogenesis and infection. The fact that NF-IL6 binds to the enhancer core sequences of various viruses strongly suggests a possible relationship of virus infection and IL-6 expression. In fact some evidence (Mahe et al. 1991, Spergel et al. 1992) indicates that NF-IL6 may interact with viral gene enhancers or viral products, although there are no definite data about the involvement of NF-IL6 in viral pathogenesis. Future studies will be required to clarify whether or not the interplay between NF-IL6 and viral infection is responsible for deregulation of the IL-6 gene.

Publication types

  • Review

MeSH terms

  • Acquired Immunodeficiency Syndrome / immunology*
  • Acute-Phase Proteins / immunology
  • Acute-Phase Reaction / immunology*
  • Amino Acid Sequence
  • Base Sequence
  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins / genetics
  • HIV Infections / immunology*
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology*
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / immunology*
  • Sequence Homology, Nucleic Acid
  • Transcription Factors / genetics
  • Virus Diseases / genetics
  • Virus Diseases / immunology*

Substances

  • Acute-Phase Proteins
  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Interleukin-6
  • Nuclear Proteins
  • Transcription Factors