title: Ultra low dose interleukin-2 therapy promotes a type 1 cytokine profile in vivo in patients with AIDS and AIDS-associated malignancies.
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.
authors.affiliation: Division of Surgery, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: V P
authors.initials: VP
authors.lastname: Khatri
authors.forename: T A
authors.initials: TA
authors.lastname: Fehniger
authors.forename: R A
authors.initials: RA
authors.lastname: Baiocchi
authors.forename: F
authors.initials: F
authors.lastname: Yu
authors.forename: M H
authors.initials: MH
authors.lastname: Shah
authors.forename: D S
authors.initials: DS
authors.lastname: Schiller
authors.forename: M
authors.initials: M
authors.lastname: Gould
authors.forename: R T
authors.initials: RT
authors.lastname: Gazzinelli
authors.forename: Z P
authors.initials: ZP
authors.lastname: Bernstein
authors.forename: M A
authors.initials: MA
authors.lastname: Caligiuri
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007113:Immunity, Innate; D016867:Immunocompromised Host / Q000187:drug effects / Q000276:immunology; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D018655:Lymphocyte Count; D016483:Lymphoma, AIDS-Related / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D016133:Polymerase Chain Reaction; D012514:Sarcoma, Kaposi / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D007376:Interleukin-2; D008070:Lipopolysaccharides; D016753:Interleukin-10; D007371:Interferon-gamma