title: BAY 50-4798, a novel, high-affinity receptor-specific recombinant interleukin-2 analog, induces dose-dependent increases in CD25 expression and proliferation among unstimulated, human peripheral blood mononuclear cells in vitro.
abstract: Interleukin-2 administration induces CD4 T cell expansion in HIV-infected patients, however, toxicity can limit dosing. BAY 50-4798 is a recombinant IL-2 analog with >1000-fold specificity for the high-affinity IL-2 receptor. The effects of this compound on unstimulated human PBMC were evaluated. PBMC from HIV(-) and HIV(+) donors were cultured in vitro with incremental doses of BAY 50-4798 or aldesleukin. CD25 expression and proliferation were evaluated with flow cytometry. Cytokine levels were measured by ELISA in culture supernatants. BAY 50-4798 induced dose-dependent increases in CD25 expression and proliferation of T cells, NK, and B cells and showed selectivity for CD4 T cells expressing CD25. Induction of pro-inflammatory cytokines was also dose-dependent and was observed at the concentrations of BAY 50-4798 with the highest biologic activity. These data suggest that BAY 50-4798 can induce proliferation of unstimulated T cells but loss of T cell selectivity and induction of pro-inflammatory cytokines occur at concentrations exerting the highest biologic activity.
authors.affiliation: Clinical and Molecular Retrovirology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Matthews
authors.forename: Sherita
authors.initials: S
authors.lastname: Chapman
authors.forename: Meena S
authors.initials: MS
authors.lastname: Ramchandani
authors.forename: H Clifford
authors.initials: HC
authors.lastname: Lane
authors.forename: Richard T
authors.initials: RT
authors.lastname: Davey
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015658:HIV Infections / Q000276:immunology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007376:Interleukin-2 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019394:Ki-67 Antigen / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D007376:Interleukin-2; D019394:Ki-67 Antigen; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; C082598:aldesleukin