Allergic Asthmatics Show Divergent Lipid Mediator Profiles from Healthy Controls Both at Baseline and following Birch Pollen ProvocationReportar como inadecuado

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Asthma is a respiratory tract disorder characterized by airway hyper-reactivity and chronic inflammation. Allergic asthma is associated with the production of allergen-specific IgE and expansion of allergen-specific T-cell populations. Progression of allergic inflammation is driven by T-helper type 2 Th2 mediators and is associated with alterations in the levels of lipid mediators.


Responses of the respiratory system to birch allergen provocation in allergic asthmatics were investigated. Eicosanoids and other oxylipins were quantified in the bronchoalveolar lumen to provide a measure of shifts in lipid mediators associated with allergen challenge in allergic asthmatics.


Eighty-seven lipid mediators representing the cyclooxygenase COX, lipoxygenase LOX and cytochrome P450 CYP metabolic pathways were screened via LC-MS-MS following off-line extraction of bronchoalveolar lavage fluid BALF. Multivariate statistics using OPLS were employed to interrogate acquired oxylipin data in combination with immunological markers.


Thirty-two oxylipins were quantified, with baseline asthmatics possessing a different oxylipin profile relative to healthy individuals that became more distinct following allergen provocation. The most prominent differences included 15-LOX-derived ω-3 and ω-6 oxylipins. Shared-and-Unique-Structures SUS-plot modeling showed a correlation R2 = 0.7 between OPLS models for baseline asthmatics R2Ycum = 0.87, Q2cum = 0.51 and allergen-provoked asthmatics R2Ycum = 0.95, Q2cum = 0.73, with the majority of quantified lipid mediators and cytokines contributing equally to both groups. Unique structures for allergen provocation included leukotrienes LTB4 and 6-trans-LTB4, CYP-derivatives of linoleic acid epoxides-diols, and IL-10.


Differences in asthmatic relative to healthy profiles suggest a role for 15-LOX products of both ω-6 and ω-3 origin in allergic inflammation. Prominent differences at baseline levels indicate that non-symptomatic asthmatics are subject to an underlying inflammatory condition not observed with other traditional mediators. Results suggest that oxylipin profiling may provide a sensitive means of characterizing low-level inflammation and that even individuals with mild disease display distinct phenotypic profiles, which may have clinical ramifications for disease.

Autor: Susanna L. Lundström, Jun Yang, Henrik J. Källberg, Sarah Thunberg, Guro Gafvelin, Jesper Z. Haeggström, Reidar Grönneberg, J



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