Effect of etanercept (Enbrel) on interleukin 6, tumor necrosis factor alpha, and markers of immune activation in HIV-infected subjects receiving interleukin 2

AIDS Res Hum Retroviruses. 2002 Jun 10;18(9):661-5. doi: 10.1089/088922202760019365.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antiretroviral Therapy, Highly Active
  • C-Reactive Protein / metabolism
  • Drug Interactions
  • Etanercept
  • HIV Infections / blood
  • HIV Infections / drug therapy
  • HIV Infections / metabolism*
  • Humans
  • Immunoglobulin G / pharmacology*
  • Immunologic Factors / pharmacology
  • Interleukin-2 / antagonists & inhibitors*
  • Interleukin-2 / therapeutic use
  • Interleukin-6 / blood*
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / therapeutic use
  • Tumor Necrosis Factor-alpha / metabolism*


  • Immunoglobulin G
  • Immunologic Factors
  • Interleukin-2
  • Interleukin-6
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein
  • Etanercept