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Research Article Free access | 10.1172/JCI2038

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

V P Khatri, T A Fehniger, R A Baiocchi, F Yu, M H Shah, D S Schiller, M Gould, R T Gazzinelli, Z P Bernstein, and M A Caligiuri

Division of Surgery, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.

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Division of Surgery, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.

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Division of Surgery, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.

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Division of Surgery, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.

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Division of Surgery, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.

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Division of Surgery, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.

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Division of Surgery, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.

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Division of Surgery, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.

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Division of Surgery, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.

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Division of Surgery, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.

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Published March 15, 1998 - More info

Published in Volume 101, Issue 6 on March 15, 1998
J Clin Invest. 1998;101(6):1373–1378. https://doi.org/10.1172/JCI2038.
© 1998 The American Society for Clinical Investigation
Published March 15, 1998 - Version history
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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-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.

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