Viral interleukin-6: role in Kaposi's sarcoma-associated herpesvirus: associated malignancies

J Interferon Cytokine Res. 2011 Nov;31(11):791-801. doi: 10.1089/jir.2011.0043. Epub 2011 Jul 18.


Viral interleukin-6 (vIL-6) is a product of Kaposi's sarcoma-associated herpesvirus (KSHV) expressed in latently infected cells and to a higher degree during viral replication. A distinctive feature of vIL-6 is the ability to directly bind and activate gp130 signaling in the absence of other receptor subunits. Secretion of vIL-6 is generally poor, but vIL-6 can activate gp130 from inside the cell. Due to the wide cell distribution of gp130, vIL-6 has the potential to induce a wide range of biological effects. Expression of vIL-6 is variable in KSHV-associated Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman's disease (MCD), and in a newly described MCD-like systemic inflammatory syndrome observed in human immunodeficiency virus-positive patients. PEL effusions usually contain vIL-6 at high concentrations; since vIL-6 induces vascular endothelial growth factor, vIL-6 likely contributes to vascular permeability and formation of PEL effusions. Lymph nodes affected with MCD contain vIL-6-positive cells, and vIL-6 levels rise in conjunction with flares of the disease and likely contribute to symptoms of inflammation. The development of vIL-6 inhibitors is a potentially important advance in the treatment of KSHV-associated malignancies where vIL-6 is expressed.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Castleman Disease / metabolism*
  • Castleman Disease / pathology
  • Castleman Disease / virology
  • Herpesvirus 8, Human / genetics
  • Herpesvirus 8, Human / metabolism*
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Lymphoma, Primary Effusion / metabolism*
  • Lymphoma, Primary Effusion / pathology
  • Lymphoma, Primary Effusion / virology
  • Sarcoma, Kaposi / metabolism*
  • Sarcoma, Kaposi / pathology
  • Sarcoma, Kaposi / virology


  • Interleukin-6