Ultra low dose interleukin-2 therapy promotes a type 1 cytokine profile in vivo in patients with AIDS and AIDS-associated malignancies

J Clin Invest. 1998 Mar 15;101(6):1373-8. doi: 10.1172/JCI2038.


This study was undertaken to determine if prolonged daily subcutaneous administration of ultra low dose IL-2 could influence the constitutive endogenous production of a type 1 (IFN-gamma) cytokine in patients with AIDS or AIDS-associated malignancies. Using a quantitative reverse transcription PCR assay, we demonstrate that daily administration of one type 1 cytokine, IL-2, for 3 mo increases significantly the constitutive endogenous gene expression of another type 1 cytokine, IFN-gamma, in vivo. The predominant source of IFN-gamma appears to be IL-2-expanded natural killer cells and CD8(+) T cells. Moreover, PBMC obtained from these patients during IL-2 therapy showed normalization of a profound deficit in IFN-gamma protein production after stimulation with extracts from infectious agents in vitro. Our data suggest that prolonged exogenous administration of a type 1 cytokine in a nontoxic fashion to patients with AIDS and AIDS-associated malignancies can enhance significantly the endogenous type 1 cytokine profile in vivo. Consequently, ultra low dose IL-2 therapy has the potential to improve the immunodeficient hosts' immune response to infectious pathogens that require IFN-gamma for clearance.

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 / metabolism
  • Acquired Immunodeficiency Syndrome / therapy*
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Flow Cytometry
  • Gene Expression
  • Humans
  • Immunity, Innate
  • Immunocompromised Host / drug effects
  • Immunocompromised Host / immunology
  • Immunotherapy / methods
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism*
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-2 / administration & dosage*
  • Interleukin-2 / therapeutic use*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Leukocytes, Mononuclear / metabolism
  • Lipopolysaccharides / immunology
  • Lymphocyte Count
  • Lymphoma, AIDS-Related / immunology
  • Lymphoma, AIDS-Related / metabolism
  • Lymphoma, AIDS-Related / therapy*
  • Polymerase Chain Reaction
  • Sarcoma, Kaposi / immunology
  • Sarcoma, Kaposi / metabolism
  • Sarcoma, Kaposi / therapy*
  • T-Lymphocyte Subsets / immunology


  • Interleukin-2
  • Lipopolysaccharides
  • Interleukin-10
  • Interferon-gamma