Interleukin (IL)-8 and Growth Related Oncogene-α in Severe Endotoxemia and the Effects of a Tumor Necrosis Factor-α/IL-1β Inhibitor on These Chemokines

Pablo Rodríguez-Wilhelmi, Ramón Montes, Akihiro Matsukawa, Verónica Hurtado, Marta Montes, José Hermida, Eduardo Rocha

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FR167653 inhibits the production of tumor necrosis factor (TNF)-α and interleukin (IL)-1β, powerful inducers of CXC chemokines IL-8 and growth related oncogene (GRO)-α. The production of IL-8 and GRO-α was investigated and the effects of FR167653 were examined in a rabbit model of endotoxin shock. Male New Zealand rabbits were given endotoxin at a dose sufficient to induce DIC. Three groups of rabbits received FR167653 at different doses. TNF-α, IL-1β, IL-8, and GRO-α levels were measured, several pathologic features were evaluated, and the results were compared with those obtained in control rabbits, which received only endotoxin. Endotoxin increased serum levels of IL-8 and GRO-α, which were associated with hypotension, renal dysfunction, and mortality, peaking at 4 h. FR167653 improved mortality, an event that was associated with decreased levels of not only TNF-α and IL-1β but also IL-8 and GRO-α. TNF-α peaked at 2 h, at a time point before IL-8 and GRO-α reached their peak, and the TNF-α level was tightly correlated with that of IL-8 and GRO-α. Altogether, these data suggest the possible involvement of IL-8 and GRO-α in endotoxin shock, and FR167653 may foster a beneficial outcome in part by modulating the chemokines level by inhibiting TNF-α and IL-1β.

Original languageEnglish
Pages (from-to)220-229
Number of pages10
JournalExperimental and Molecular Pathology
Issue number3
Publication statusPublished - Dec 2002
Externally publishedYes



  • Endotoxin shock
  • FR167653
  • Growth related oncogene-α
  • Interleukin-1β
  • Interleukin-8
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Pathology and Forensic Medicine

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