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

Vijay P. Khatri, Todd A. Fehniger, Robert A. Baiocchi, Feng Yu, Manisha H. Shah, Daryl S. Schiller, Margaret Gould, Ricardo T. Gazzinelli, Zale P. Bernstein, Michael A. Caligiuri

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

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-γ) 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-γ, in vivo. The predominant source of IFN-γ 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-γ 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-γ for clearance.

Original languageEnglish (US)
Pages (from-to)1373-1378
Number of pages6
JournalJournal of Clinical Investigation
Volume101
Issue number6
StatePublished - Mar 15 1998
Externally publishedYes

Keywords

  • AIDS
  • Immunotherapy
  • Interferon-γ
  • Interleukin-2
  • Natural immunity

ASJC Scopus subject areas

  • Medicine(all)

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    Khatri, V. P., Fehniger, T. A., Baiocchi, R. A., Yu, F., Shah, M. H., Schiller, D. S., Gould, M., Gazzinelli, R. T., Bernstein, Z. P., & Caligiuri, M. A. (1998). Ultra low dose interleukin-2 therapy promotes a type I cytokine profile in vivo in patients with AIDS and AIDS-associated malignancies. Journal of Clinical Investigation, 101(6), 1373-1378.