Reparixin, a specific interleukin-8 inhibitor, has no effects on inflammation during endotoxemia.
Int J Immunopathol Pharmacol
; 20(1): 25-36, 2007.
Article
em En
| MEDLINE
| ID: mdl-17346425
ABSTRACT
Reparixin antagonizes interleukin-8 (IL-8) on the level of signal transduction in vitro. We hypothesized that IL-8 mediates some of the reactions occurring during acute inflammation and specifically that IL-8 may be a mediator of endotoxin induced neutrophilia. We therefore tested the effects of reparixin on humoral and cellular parameters in LPS-induced acute systemic inflammation. The study is a randomized (32 activeplacebo), double-blind, placebo-controlled parallel group trial. Twenty healthy male volunteers randomly received either reparixin (12) or placebo (8) intravenously. One hour after the start of reparixin/placebo infusion a bolus of 2 ng/kg endotoxin was infused over 1-2 min. Blood samples were obtained over 24 h. Reparixin, being metabolized to ibuprofen, suppressed serum thromboxane B2 levels by 78 percent compared to baseline and control at 8 h. LPS-induced neutrophilia was not significantly affected by reparixin in human volunteers. Consistently, reparixin did not alter the lymphocyte or monocyte counts and had no effect on LPS-induced systemic inflammation as measured by tumor necrosis factor alpha (TNF-alpha) or interleukin-6 (IL-6) release. Regulation of IL-8 receptors CXCR1 and 2 and the degranulation marker CD11b showed the expected kinetics. Reparixin had no effect on thrombin formation as measured by prothrombin fragment (F1+2). In conclusion, our study showed that reparixin was safe but had no impact on endotoxin induced inflammation. In contrast to previous studies with its metabolite ibuprofen, reparixin does not enhance inflammation in this model.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
/
Interleucina-8
/
Endotoxemia
/
Inflamação
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Int J Immunopathol Pharmacol
Ano de publicação:
2007
Tipo de documento:
Article