Interleukin-8 stimulates human immunodeficiency virus type 1 replication and is a potential new target for antiretroviral therapy

J Virol. 2001 Sep;75(17):8195-202. doi: 10.1128/jvi.75.17.8195-8202.2001.

Abstract

Production of the C-X-C chemokines interleukin-8 (IL-8) and growth-regulated oncogene alpha (GRO-alpha) in macrophages is stimulated by exposure to human immunodeficiency virus type 1 (HIV-1). We have demonstrated previously that GRO-alpha then stimulates HIV-1 replication in both T lymphocytes and macrophages. Here we demonstrate that IL-8 also stimulates HIV-1 replication in macrophages and T lymphocytes. We further show that increased levels of IL-8 are present in the lymphoid tissue of patients with AIDS. In addition, we demonstrate that compounds which inhibit the actions of IL-8 and GRO-alpha via their receptors, CXCR1 and CXCR2, also inhibit HIV-1 replication in both T lymphocytes and macrophages, indicating potential therapeutic uses for these compounds in HIV-1 infection and AIDS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acquired Immunodeficiency Syndrome / immunology
  • Acquired Immunodeficiency Syndrome / virology*
  • Antibodies / immunology
  • Chemokine CXCL1
  • Chemokines, CXC*
  • Chemotactic Factors / antagonists & inhibitors
  • Chemotactic Factors / pharmacology
  • Growth Substances / pharmacology
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Intercellular Signaling Peptides and Proteins*
  • Interleukin-8 / antagonists & inhibitors
  • Interleukin-8 / immunology
  • Interleukin-8 / metabolism
  • Interleukin-8 / pharmacology*
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / metabolism
  • Macrophages / virology*
  • Monocytes
  • Phenylurea Compounds / pharmacology
  • Receptors, Interleukin-8A / immunology
  • Receptors, Interleukin-8B / immunology
  • T-Lymphocytes / virology*
  • Virus Replication / drug effects

Substances

  • Antibodies
  • CXCL1 protein, human
  • Chemokine CXCL1
  • Chemokines, CXC
  • Chemotactic Factors
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-8
  • Phenylurea Compounds
  • Receptors, Interleukin-8A
  • Receptors, Interleukin-8B
  • SB 225002