title: Effect of etanercept (Enbrel) on interleukin 6, tumor necrosis factor alpha, and markers of immune activation in HIV-infected subjects receiving interleukin 2.
abstract: The effect of etanercept, a soluble p75 tumor necrosis factor (TNF) receptor:Fc fusion protein (Enbrel; Immunex, Seattle, WA) on plasma cytokines was evaluated in 11 HIV-infected subjects receiving highly active antiretroviral therapy (HAART) for 28 weeks with or without subcutaneous or intravenous recombinant human interleukin 2 (rhIL-2). Plasma IL-6 and C-reactive protein (CRP) levels increased after rhIL-2 treatment. Etanercept pretreatment attenuated these increases. Median plasma IL-6 levels were 20.29 pg/ml 4 days after rhIL-2 and 7.87 pg/ml 4 days after etanercept and rhIL-2 (p = 0.22); median CRP levels were 78.73 and 46.16 microg/ml, respectively (p = 0.03). An effect on TNF bioactivity could not be assessed as all measurements were below limits of detection. No significant changes were seen in temperature or plasma levels of IL-4, IL-10, IL-12, interferon gamma, or HIV-1 RNA levels. All subjects had undetectable or low-level HIV-1 RNA levels before etanercept dosing. One subject died; however, her death was thought to be unrelated to etanercept. Pretreatment with etanercept may blunt activation of IL-6 and CRP expression induced by rhIL-2. The safety and utility of etanercept in HIV-infected persons should be explored further.
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Rush Medical College, Chicago, Illinois 60612-3833, USA. bsha@rush.edu
authors.forename: Beverly E
authors.initials: BE
authors.lastname: Sha
authors.forename: Hernan
authors.initials: H
authors.lastname: Valdez
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Gelman
authors.forename: Alan L
authors.initials: AL
authors.lastname: Landay
authors.forename: Jan
authors.initials: J
authors.lastname: Agosti
authors.forename: Ronald
authors.initials: R
authors.lastname: Mitsuyasu
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pollard
authors.forename: Donna
authors.initials: D
authors.lastname: Mildvan
authors.forename: Ann
authors.initials: A
authors.lastname: Namkung
authors.forename: Debra M
authors.initials: DM
authors.lastname: Ogata-Arakaki
authors.forename: Lawrence
authors.initials: L
authors.lastname: Fox
authors.forename: Scharla
authors.initials: S
authors.lastname: Estep
authors.forename: Alejo
authors.initials: A
authors.lastname: Erice
authors.forename: Patrick
authors.initials: P
authors.lastname: Kilgo
authors.forename: Robert E
authors.initials: RE
authors.lastname: Walker
authors.forename: Lynne
authors.initials: L
authors.lastname: Bancroft
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D002097:C-Reactive Protein / Q000378:metabolism; D004347:Drug Interactions; D000068800:Etanercept; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D007074:Immunoglobulin G; D007155:Immunologic Factors; D007376:Interleukin-2; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000068800:Etanercept