Effects of subcutaneous interleukin-2 therapy on CD4 subsets and in vitro cytokine production in HIV+ subjects

Paolo De Paoli, Stefania Zanussi, Cecilia Simonelli, Maria Teresa Bortolin, Monica D'Andrea, Cinzia Crepaldi, Renato Talamini, Manola Comar, Mauro Giacca, Umberto Tirelli

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Abstract

HIV infection is characterized by the reduction of the CD4+, CD45RA+, CD26+, and CD28+ lymphocyte subsets and of the in vitro production of IL-2, IL-4, and interferon-γ; on the contrary, chemokine production is usually increased. These abnormalities are only partially restored by antiretroviral chemotherapy. Therapy with interleukin-2 has been proposed to restore the functions of the immune system, but the mechanisms by which IL-2 exerts its activities are unknown. The aim of this study was to define the effects of rIL-2 administration on CD4+, CD45RA+, CD45R0+, and CD26+ lymphocytes and on the in vitro production of IL-2, IL-4, IL-10, IFN-γ, RANTES, and sCD30 in HIV+ patients. 10 HIV+ patients with CD4 cell counts between 200 and 500 cells/mm3 were treated with six cycles of subcutaneous recombinant IL-2 administration, in combination with zidovudine and didanosine. This therapeutic regimen resulted in a remarkable increase in the number of CD4+ cells and in the prolonged reduction of the levels of viremia. CD45R01 cells were expanded during the first cycle of therapy, while CD45RA+/CD26+ cells predominated after the third cycle. At this time, the in vitro production of IL-2, IL-4, IFN-γ, and sCD30 were significantly upregulated. These results demonstrate that rIL-2 in HIV+ patients induces the reconstitution of the CD4/CD45RA lymphocytes subtype. This expanded cell population recovered the ability to produce in vitro IL-2, IL-4, and IFN-γ. These effects may be beneficial to HIV+ patients by improving their immune response to microorganisms or vaccines.

Original languageEnglish
Pages (from-to)2737-2743
Number of pages7
JournalJournal of Clinical Investigation
Volume100
Issue number11
Publication statusPublished - Dec 1 1997

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Keywords

  • CD4-positive T- lymphocytes
  • Cytokines
  • HIV infection
  • HIV viremia
  • Interleukin-2 injections

ASJC Scopus subject areas

  • Medicine(all)

Cite this

De Paoli, P., Zanussi, S., Simonelli, C., Bortolin, M. T., D'Andrea, M., Crepaldi, C., Talamini, R., Comar, M., Giacca, M., & Tirelli, U. (1997). Effects of subcutaneous interleukin-2 therapy on CD4 subsets and in vitro cytokine production in HIV+ subjects. Journal of Clinical Investigation, 100(11), 2737-2743.