Journal
BMC PHARMACOLOGY & TOXICOLOGY
Volume 15, Issue -, Pages -Publisher
BMC
DOI: 10.1186/2050-6511-15-60
Keywords
Endotoxin inhalation; Neutrophilic inflammation; Corticosteroids; Anti-TNF
Categories
Funding
- Belgium CUD (Commission Universitaire au Developpement)
- Funxional Therapeutics Ltd, Cambridge, United Kingdom
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Background: Inhaled endotoxin induces airways'neutrophilia, in human. TNF-a being a key cytokine in the response to endotoxin, the effect of anti-TNF on the endotoxin-induced neutrophilic response was evaluated among healthy volunteers. Methods: Among a population of 30 healthy subjects, an induced-sputum was collected 2 weeks before, and 24 hours after an inhalation of 20 mcg endotoxin (E coli 026:B6). Then, the subjects were randomized into 3 parallel groups treated with control, oral methylprednisolone 20 mg/day during 7 days or anti-TNF (adalimumab, Humira (R), Abbott) 40 mg SC. One week later, an induced-sputum was sampled, 24 hours after an inhalation of endotoxin. Results: After endotoxin inhalation, the number of total cells, neutrophils and macrophages was significantly increased (p <0.001). Compared to the response to endotoxin among the control group, anti-TNF inhibited the endotoxin-induced neutrophil influx, both in relative (51.3 (+/- 6.4)% versus 26.2 (+/- 5.3)%, p <0.002) and in absolute values (1321 (443-3935) cells/mcL versus 247 (68-906) cells/mcL, p <0.02). The endotoxin-induced neutrophilic response was not significantly modified among the control group and oral corticosteroid group. Conclusions: While oral corticosteroid had no effect, anti-TNF inhibited the neutrophil influx in sputum, induced by inhalation of endotoxin, in human subject. The endotoxin model could be an early predictor of clinical efficacy of novel therapeutics.
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