Interleukin (IL)-8 and growth related oncogene-alpha in severe endotoxemia and the effects of a tumor necrosis factor-alpha/IL-1beta inhibitor on these chemokines

FR167653 inhibits the production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, powerful inducers of CXC chemokines IL-8 and growth related oncogene (GRO)-alpha. The production of IL-8 and GRO-alpha was investigated and the effects of FR167653 were examined in a rabbit model of end...

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Detalles Bibliográficos
Autores: Rodriguez-Wilhelmi, P. (Pablo)|||/items/2f865af7-538c-4328-abbd-1c032d3ffacd, Montes, R. (Ramón)|||/items/8f33031a-c4c2-48c3-beb6-0177898ba38d, Matsukawa, A. (Akihiro)|||/items/ca64791a-cee5-4079-b1a3-8be15260b663, Hurtado, V. (Verónica)|||/items/ffd47744-abb4-4151-a9d4-b83d26adad46, Montes-Resano, M. (Marta)|||/items/a4f2bd35-a15c-47ff-a3db-2ca1c35dcdde, Hermida-Santos, J. (José)|||/items/9e67bdb3-d55d-4819-847e-9b44cc487fdb, Rocha, E. (Eduardo)|||/items/96d5cf13-d967-4252-8888-36a4956209d6
Tipo de recurso: artículo
Fecha de publicación:2002
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/22118
Acceso en línea:https://hdl.handle.net/10171/22118
Access Level:acceso abierto
Palabra clave:Endotoxin shock
Interleukin-8
Growth related oncogene-α
Tumor necrosis factor-α
Interleukin-1β
FR167653
Descripción
Sumario:FR167653 inhibits the production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, powerful inducers of CXC chemokines IL-8 and growth related oncogene (GRO)-alpha. The production of IL-8 and GRO-alpha 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-alpha, IL-1beta, IL-8, and GRO-alpha 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-alpha, 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-alpha and IL-1beta but also IL-8 and GRO-alpha. TNF-alpha peaked at 2 h, at a time point before IL-8 and GRO-alpha reached their peak, and the TNF-alpha level was tightly correlated with that of IL-8 and GRO-alpha. Altogether, these data suggest the possible involvement of IL-8 and GRO-alpha in endotoxin shock, and FR167653 may foster a beneficial outcome in part by modulating the chemokines level by inhibiting TNF-alpha and IL-1beta.

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