Effect of etanercept (Enbrel) on interleukin 6, tumor necrosis factor alpha, and markers of immune activation in HIV-infected subjects receiving interleukin 2.
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.
Sha
Beverly E
BE
Section of Infectious Diseases, Department of Medicine, Rush Medical College, Chicago, Illinois 60612-3833, USA. bsha@rush.edu
Valdez
Hernan
H
Gelman
Rebecca S
RS
Landay
Alan L
AL
Agosti
Jan
J
Mitsuyasu
Ronald
R
Pollard
Richard B
RB
Mildvan
Donna
D
Namkung
Ann
A
Ogata-Arakaki
Debra M
DM
Fox
Lawrence
L
Estep
Scharla
S
Erice
Alejo
A
Kilgo
Patrick
P
Walker
Robert E
RE
Bancroft
Lynne
L
Lederman
Michael M
MM
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*
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