Abstract
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 language | English |
|---|---|
| Pages (from-to) | 220-229 |
| Number of pages | 10 |
| Journal | Experimental and Molecular Pathology |
| Volume | 73 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Dec 2002 |
| Externally published | Yes |
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Keywords
- 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
Cite this
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. / Rodríguez-Wilhelmi, Pablo; Montes, Ramón; Matsukawa, Akihiro; Hurtado, Verónica; Montes, Marta; Hermida, José; Rocha, Eduardo.
In: Experimental and Molecular Pathology, Vol. 73, No. 3, 12.2002, p. 220-229.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Rodríguez-Wilhelmi, Pablo
AU - Montes, Ramón
AU - Matsukawa, Akihiro
AU - Hurtado, Verónica
AU - Montes, Marta
AU - Hermida, José
AU - Rocha, Eduardo
PY - 2002/12
Y1 - 2002/12
N2 - 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.
AB - 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.
KW - Endotoxin shock
KW - FR167653
KW - Growth related oncogene-α
KW - Interleukin-1β
KW - Interleukin-8
KW - Tumor necrosis factor-α
UR - http://www.scopus.com/inward/record.url?scp=0036981588&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036981588&partnerID=8YFLogxK
U2 - 10.1006/exmp.2002.2467
DO - 10.1006/exmp.2002.2467
M3 - Article
VL - 73
SP - 220
EP - 229
JO - Experimental and Molecular Pathology
JF - Experimental and Molecular Pathology
SN - 0014-4800
IS - 3
ER -