Anti-TNF inhibits the Airways neutrophilic inflammation induced by inhaled endotoxin in human

BMC Clinical Pharmacology

Francis Corazza³  Virginie Doyen²  Phong Huy Duc Dinh¹  Olivier Michel² 

[1]Department of Immunology, Pham Ngoc Thach University of Medicine (PNTU), Ho Chi Minh, Vietnam

[2]Clinic of Allergology and Immunology, CHU Brugmann (Université Libre de Bruxelles - ULB), 4 pl Van Gehuchten, B -1020, Brussels, Belgium

[3]Laboratory of Immunology, CHU Brugmann (Université Libre de Bruxelles - ULB), Brussels, Belgium

关键词: Anti-TNF;    Corticosteroids;    Neutrophilic inflammation;    Endotoxin inhalation;   

Others  :  1084633
DOI  :  10.1186/2050-6511-15-60

 received in 2014-03-07, accepted in 2014-10-14,  发布年份 2014

【 摘 要 】

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®, 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.

Trial registration

ClinicalTrials.govNCT02252809 (EudraCT2008-005526-37)

【 授权许可】

   
2014 Michel et al.; licensee BioMed Central Ltd.

【 图 表 】

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