Published ahead of print on November 25, 2003, doi:10.1164/rccm.200301-104OC
Am. J. Respir. Crit. Care Med., Volume 169, Number 5, March 2004, 578-586
A more recent version of this article appeared on March 1, 2004
Submitted on January 27, 2003
Accepted on November 24, 2003
Natural porcine surfactant augments airway inflammation after allergen challenge in asthmatics
Veit J Erpenbeck1, Andreas Hagenberg2, Yasmin Dulkys3, Jorn Elsner3, Ralf Balder4, Harald Krentel2, Marc Discher2, Armin Braun4, Norbert Krug4, and Jens M Hohlfeld1*
1 Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany; Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany,
2 Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany,
3 Department of Dermatology and Allergology, Hannover Medical School, Hannover, Germany,
4 Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany
* To whom correspondence should be addressed. E-mail: hohlfeld{at}item.fhg.de.
There is increasing evidence for a role of pulmonary surfactant in asthma and allergic inflammation. In murine asthma models recent studies have demonstrated that surfactant components down-regulate the allergic inflammation. Therefore, we tested the hypothesis that in mild asthmatics a natural porcine surfactant preparation (Curosurf®) given prior to segmental allergen challenge can reduce the allergic airway inflammation. Ten asthmatic patients and five healthy controls were treated in two segments with either Curosurf® or vehicle followed by local allergen challenge. Six additional asthmatic patients received Curosurf® prior to allergen challenge in one segment as above, but the second segment was instilled with Curosurf® without allergen challenge. Unexpectedly, surfactant treatment augmented the eosinophilic inflammation 24 hours after allergen challenge. A direct chemotactic effect of Curosurf® was excluded. However, levels of eotaxin and IL-5 were increased in BAL after Curosurf® treatment while IFN- -levels and numbers of IFN-+ T cells were decreased. Curosurf® had no influence on spreading and retention of allergen determined by allergen uptake in mice. These findings demonstrate that treatment with a natural porcine surfactant results in an augmentation of the eosinophilic inflammation after allergen challenge that is more likely due to immunomodulatory effects than to biophysical properties of the surfactant.
Key words: asthma, allergy, immunomodulation, pulmonary surfactant, segmental allergen provocation
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