Effects of a cytokine inhibitor, JTE-607, on the response to endotoxin in healthy human volunteers.
Int Immunopharmacol
; 11(11): 1837-43, 2011 Nov.
Article
en En
| MEDLINE
| ID: mdl-21820084
ABSTRACT
It is generally regarded that the excessive production of cytokines plays an important role in the pathology of autoimmune diseases and septic shock. We have investigated the ability of JTE-607, a novel inhibitor of cytokine production, to modulate the inflammatory response to endotoxin in healthy human volunteers. Three cohorts of healthy male volunteers were recruited for a randomized, placebo-controlled, double-blind study. Within each cohort, 6 subjects received a single 8-hour intravenous infusion of JTE-607 (either 0.03, 0.1 or 0.3 mg/kg/h) and 3 subjects received a placebo infusion. Two hours after the start of the JTE-607 infusion, all subjects received a 30 unit/kg bolus infusion of endotoxin. JTE-607 administration resulted in the decrease in endotoxin-induced IL-10 production with mean % difference from placebo of -79.5% (P=0.040) and -86.2% (P=0.026) at 0.1 and 0.3 mg/kg/h dose, respectively. The production of endotoxin-mediated interleukin (IL)-1 receptor antagonist was significantly inhibited at 0.3 mg/kg/h dose with mean % difference from placebo of -60% (P=0.0037). Endotoxin-induced C-reactive protein decreased with the increasing dose of JTE-607 with mean % difference from placebo of -32.1% (P=0.322), -82.9% (P=0.0001) and -90.3% (P<0.0001) at 0.03, 0.1 and 0.3 mg/kg/h dose, respectively. In conclusion, this study describes a cytokine modulator JTE-607, which inhibits production of IL-10, IL-1ra and C-reactive protein in a human model of endotoxemia.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Fenilalanina
/
Piperazinas
/
Lipopolisacáridos
/
Citocinas
Tipo de estudio:
Clinical_trials
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adolescent
/
Adult
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Int Immunopharmacol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Reino Unido