Repeated low-dose allergen exposure induces an allergic airway inflammation in asthmatic subjects. The inflammation is associated with an altered AM phenotype pattern, consistent with an influx of monocytes and a hypothetical increased accessory cell function in the airways, possibly contributing to the development and sustenance of airway inflammation in asthma.

Immune and inflammatory responses mediated by cytokines are essential in the pathophysiology of asthma. The aim of this study was to analyse the cytokine mRNA profiles in bronchoalveolar lavage (BAL) cells of patients with mild atopic asthma, before and after induction of a subclinical allergic airway inflammation. For this purpose, eight patients with mild atopic asthma received low-dose allergen inhalations equivalent to 10% of a provocational dose causing a 20% fall in forced expiratory flow in 1 sec (PD20) for 7 weekdays. BAL was performed before and after low-dose provocations in patients, and without provocation in five healthy controls. Alveolar macrophages (AM) were enriched by negative selection, using magnetic beads, to enable separate studies of the BAL cells. Using a semiquantitative RT-PCR technique, the mRNA expression of macrophage-derived cytokines interleukin (IL)-1, IL-6, IL-8, IL-10, IL-12, IL-13, interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta was analysed. After low-dose provocations, we observed a significant increase in the expression of IL-13 mRNA (P = 0.01) in BAL cells enriched for AM of the asthmatic patients. The increased IL-13 mRNA positively correlated with the proportion of BAL fluid eosinophils (r = 0.7, P = 0.05). Moreover, a tendency was found towards an increased IL-1 and a reduced IL-6, IL-8, IFN-gamma and TNF-alpha expression by the BAL cells. Comparing asthmatic patients before low-dose provocations and healthy controls, a significantly higher expression of IL-6 (P<0.003), IL-10 (P<0.005) and TGF-beta (P<0.003) and a significantly lower expression of IL-8 (P<0.005) and TNF-alpha (P<0.01) was detected in the patients. In summary, repeated low-dose allergen provocations of asthmatic patients results in a modified BAL cell cytokine mRNA profile with increased production of IL-13, that may be of importance for the development of a Th2-like immune response. A possible source of the increased IL-13 mRNA is AM, which may have a more active function in the allergic inflammation than previously thought.

Allergy is associated with non-specific symptoms such as fatigue, sleep problems and impaired cognition. One explanation could be that the allergic inflammatory state includes activation of immune cells in the brain, but this hypothesis has not been tested in humans. The aim of the present study was therefore to investigate seasonal changes in the glial cell marker translocator protein (TSPO), and to relate this to peripheral inflammation, fatigue and sleep, in allergy. We examined 18 patients with severe seasonal allergy, and 13 healthy subjects in and out-of pollen season using positron emission tomography (n = 15/13) and the TSPO radioligand [C]PBR28. In addition, TNF-α, IL-5, IL-6, IL-8 and IFN-γ were measured in peripheral blood, and subjective ratings of fatigue and sleepiness as well as objective and subjective sleep were investigated. No difference in levels of TSPO was seen between patients and healthy subjects, nor in relation to pollen season. However, allergic subjects displayed both increased fatigue, sleepiness and increased percentage of deep sleep, as well as increased levels of IL-5 and TNF-α during pollen season, compared to healthy subjects. Allergic subjects also had shorter total sleep time, regardless of season. In conclusion, allergic subjects are indicated to respond to allergen exposure during pollen season with a clear pattern of behavioral disruption and peripheral inflammatory activation, but not with changes in brain TSPO levels. This underscores a need for development and use of more specific markers to understand brain consequences of peripheral inflammation that will be applicable in human subjects.

The Clara cell 16 kDa protein (CC16) maps to an atopy-associated region of chromosome 11 and has been ascribed an anti-inflammatory function. Using reverse-phase HPLC and Western blot analysis, we have evaluated the polypeptide pattern in bronchoalveolar lavage (BAL) fluid retrieved from asthmatics, before and after induction of airway inflammation by low-dose allergen inhalation challenge. A prominent decrease of CC16 was seen after induction of inflammation, and a further CC16 decrease was observed in lavage fluid where surfactant had been removed. Reduced levels of pulmonary CC16 may cause loss of anti-inflammatory activity in the airways and contribute to the development of airway inflammation in asthma.