Anti-ovine interleukin-1beta monoclonal antibody immunotherapy in an ovine model of gram-negative septic shock.
Crit Care Med
; 30(1): 171-81, 2002 Jan.
Article
em En
| MEDLINE
| ID: mdl-11902259
ABSTRACT
OBJECTIVE:
To investigate the efficacy of an anti-ovine interleukin-1beta monoclonal antibody to ameliorate pathophysiological derangements and improve survival in an ovine model of gram-negative septic shock.DESIGN:
Prospective, placebo-controlled, interventional study (24-hr study period).SETTING:
University hospital animal research laboratory.SUBJECTS:
Ten awake, mature female sheep.INTERVENTIONS:
Seven milligrams per kilogram of intravenous anti-ovine interleukin-1beta immunoglobin G1 monoclonal antibody (anti-interleukin-1beta group, n = 5) or equivalent amount of protein (5% human albumin; control group, n = 5) was infused over 1 hr (time-zero minus 1 hr to time-zero) and followed by an intravenous LD100 live Escherichia coli infusion (time-zero to time-zero plus 1 hr). Normal saline, maintenance and boluses to maintain baseline filling pressures, and gentamicin, 3 mg/kg intravenous, at time-zero plus 2 and time-zero plus 13 hrs. MEASUREMENTS AND MAINRESULTS:
Hemodynamic and oxygen transport indexes as well as hematological, biochemical, cytokine (interleukin-1beta, tumor necrosis factor-alpha), and endotoxin measurements were performed at baseline (time-zero minus 1 hr), on completion of the monoclonal antibody/placebo (time-zero) and E. coli (time-zero plus 1 hr) infusions, and at multiple time points thereafter (time-zero plus 1.5 hrs to time-zero plus 24 hrs). Baseline data were not different between the treatment groups. From time-zero plus 1.5 hrs onward, in the anti-interleukin-1beta group, there was a sustained increase in mean arterial pressure, decreased peripheral vasodilation, and an attenuated metabolic acidosis, relative to the control group (p < or = .01, repeated-measures analysis of variance). Predicted percentage increases in mean arterial pressure and systemic vascular resistance index relative to the control group were 35% and 40%, respectively. Resuscitation fluid requirements were also decreased anti-interleukin-1beta group, 4.1 +/- 2.9 mL x kg(-1) x hr(-1); control group, 10.6 +/- 1.8 mL x kg(-1) x hr(-1) (p < or = .01, Student's t-test). Survival was not different (anti-interleukin-1beta group, 40%; control group, 0%; p > .01, log-rank test).CONCLUSIONS:
Adjunctive therapy with anti-ovine interleukin-1beta monoclonal antibody in ovine gram-negative septic shock was associated with improved hemodynamic performance. However, the beneficial effects were incomplete and survival was not significantly improved.
Buscar no Google
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
/
3_ND
Base de dados:
MEDLINE
Assunto principal:
Choque Séptico
/
Interleucina-1
/
Infecções por Bactérias Gram-Negativas
/
Anticorpos Monoclonais
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Crit Care Med
Ano de publicação:
2002
Tipo de documento:
Article