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Pneumologia/Pulmão

Aumento da produção de TNF-a em portadores de asma refratária

06/04/2006

 

 

Tem sido possível a investigação das citocinas na asma refratária e também dos antagonistas de produção do fator de necrose tumoral alfa. Neste trabalho foi demonstrado evidências desta função do fator de necrose tumoral alfa e a asma refratária.

Foi concluído que há uma forte regulação do eixo produtor de fator de necrose tumoral alfa e a refratariedade da asma.

Evidence of a Role of Tumor Necrosis Factor in Refractory Asthma

Mike A. Berry, M.R.C.P., Beverley Hargadon, R.G.N., Maria Shelley, R.G.N., B.A., Debbie Parker, B.Sc., Dominick E. Shaw, M.R.C.P., Ruth H. Green, M.D., M.R.C.P., Peter Bradding, D.M., F.R.C.P., Christopher E. Brightling, Ph.D., M.R.C.P., Andrew J. Wardlaw, Ph.D., F.R.C.P., and Ian D. Pavord, D.M., F.R.C.P.

 

Volume 354:697-708

February 16, 2006

Number 7

 

ABSTRACT

Background The development of tumor necrosis factor (TNF- ) antagonists has made it feasible to investigate the role of this cytokine in refractory asthma.

Methods We measured markers of TNF- activity on peripheral-blood monocytes in 10 patients with refractory asthma, 10 patients with mild-to-moderate asthma, and 10 control subjects. We also investigated the effects of treatment with the soluble TNF- receptor etanercept (25 mg twice weekly) in the patients with refractory asthma in a placebo-controlled, double-blind, crossover pilot study.

Results As compared with patients with mild-to-moderate asthma and controls, patients with refractory asthma had increased expression of membrane-bound TNF- , TNF- receptor 1, and TNF- –converting enzyme by peripheral-blood monocytes. In the clinical trial, as compared with placebo, 10 weeks of treatment with etanercept was associated with a significant increase in the concentration of methacholine required to provoke a 20 percent decrease in the forced expiratory volume in one second (FEV1) (mean difference in doubling concentration changes between etanercept and placebo, 3.5; 95 percent confidence interval, 0.07 to 7.0; P=0.05), an improvement in the asthma-related quality-of-life score (by 0.85 point; 95 percent confidence interval, 0.16 to 1.54 on a 7-point scale; P=0.02), and a 0.32-liter increase in post-bronchodilator FEV1 (95 percent confidence interval, 0.08 to 0.55; P=0.01).

Conclusions Patients with refractory asthma have evidence of up-regulation of the TNF- axis. (ClinicalTrials.gov number, NCT00276029 [ClinicalTrials.gov] .)


Source Information

From the Institute for Lung Health, University Hospital of Leicester National Health Service Trust, Glenfield Hospital, Leicester, United Kingdom.

Address reprint requests to Prof. Pavord at the Institute for Lung Health, University Hospital of Leicester National Health Service Trust, Glenfield Hospital, Groby Rd., Leicester LE3 9QP, United Kingdom, or at ian.pavord@uhl-tr.nhs.uk .

http://content.nejm.org/cgi/content/abstract/354/7/697

 


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