Olfactory cues of naturally occurring systemic inflammation: A pilot study of seasonal allergy

Introduction: In an attempt to avoid contact with infectious individuals, humans likely respond to generalised rather than specific markers of disease. Humans may thus perceive a non-infectious individual as socially less attractive if they look (e.g., have facial discoloration), move (e.g., have a slower walking pace), or sound (e.g., sneeze) sick. This pilot study tested whether humans are averse to the body odour of non-infectious individuals with a low-grade systemic inflammation. Methods: We collected the axillary body odour of individuals with severe seasonal allergy (N = 14) and healthy controls (N = 10) during and outside the allergy season and measured serum levels of two inflammatory cytokines (tumor necrosis factor-α, interleukin-5). Independent participants (N = 67) then sampled and rated these odours on intensity and pleasantness. Results: While individuals with seasonal allergy had nominally more unpleasant and intense body odours during the allergy season - relative to outside of the allergy season and to healthy controls - these effects were not significant. When examining immune markers, the change in perceived pleasantness of an individual’s body odour (from out- to inside pollen season), was significantly related to the change in their interleukin-5 levels but not to tumor necrosis factor-α. Discussion: Our findings tentatively suggest that the human olfactory system could be sensitive to inflammation as present in a non-communicable condition. Larger replications are required to determine the role of olfaction in the perception of infectious and non-infectious (e.g., chronic diseases) conditions.publishedVersio

Early airway inflammation in allergic asthma : aspects of pulmonary innate immunity

Allergic asthma is a chronic disease in which allergen-induced inflammatory processes of the airways contribute to the development of symptoms and eventually may lead to remodeling of the airway tissue. In the present work low-dose allergen inhalation challenges of individuals with asthma were used as a model to delineate inflammatory events occurring in an early phase of the allergic airway inflammation associated with asthma. The thesis focuses on studies of the pulmonary innate immune system in this context, specifically alveolar macrophages and their mediators as well as anti-inflammatory and antibacterial peptides and proteins. Low-dose allergen exposure of asthmatic subjects induced an asymptomatic allergic airway inflammation, characterized by increased bronchial reactivity and increased numbers of total cells and eosinophils in BAL fluid, accompanied by raised levels of ECP in serum. The macrophage expression of surface antigens as well as the expression of cytokines by BAL cells enriched for alveolar macrophages was investigated using flow cytometry and RT-PCR respectively. An altered alveolar macrophage phenotype pattern consistent with an increased proportion of monocytes within the population and increased mRNA levels of IL-13 were found following allergen exposure. The feasibility of induced sputum as a method to recruit and study pulmonary macrophages was evaluated. Induced sputum retrieved from healthy individuals was found to provide a lower total number of cells showing a differential distribution of cell populations and a differing macrophage phenotype pattern compared to material collected with BAL. To identify disease-associated alterations of the BAL fluid polypeptide pattern after induction of allergic airway inflammation, BAL fluid enriched for polypeptides was fractionated and investigated using RP-HPLC, Western blot and structural analyses. Decreased post-challenge levels of the anti-inflammatory protein CC16 were found, indicating a loss of anti-inflammatory activity in the airways in an early phase of the airway inflammation in asthma. To investigate effects of an induced allergic inflammation on parts of the pulmonary antimicrobial defense system, antibacterial components in BAL fluid derived from asthmatics and controls were analyzed using an in vitro bio-assay and structural analyses. Similar levels of antibacterial activity were found and several active components were identified in BAL fluid retrieved from asthmatics before and after allergen challenges. Comparing antibacterial profiles of non-challenged asthmatics to that of healthy individuals, we found a larger number of antibacterial components together with higher levels of baseline activity in the patients, indicating that allergic asthma is associated with an augmented pulmonary expression of antibacterial components. In conclusion, early stage allergic airway inflammation is associated with an altered balance of pro- and anti-inflammatory effectors of innate immunity, likely to be of importance in the further development of airway inflammation in asthma

Objective and Subjective Sleep in Rheumatoid Arthritis and Severe Seasonal Allergy : Preliminary Assessments of the Role of Sickness, Central and Peripheral Inflammation

Introduction: Disturbed sleep in inflammatory disorders such as allergy and rheumatoid arthritis (RA) is common and may be directly or indirectly related to disease processes, but has not been well characterized in these patient groups, especially not with objective methods. Aim: The present study aimed to characterize objective and subjective sleep in patients with allergy or RA using sleep diaries, one-channel EEG and actigraphy. It also aimed to investigate if sleep measures were associated with central immune activation, assessed using translocator protein (TSPO) positron emission tomography, as well as cytokine markers of peripheral inflammation and disease-specific symptoms or general symptoms of sickness. Methods: In total, 18 patients with seasonal pollen allergy, 18 patients with RA and 26 healthy controls were included in the study. Allergy patients and matched controls were assessed twice, in and out of pollen season, and RA patients and controls were assessed once. Sleep was recorded for approximately 1 week at each occasion. Results: Patients with allergy had increased levels of slow-wave sleep during pollen season. In contrast, patients with RA had less SWS compared to healthy controls, while no differences were observed in sleep duration or subjective sleep quality. Across groups, neither proinflammatory cytokines, grey matter TSPO levels nor general sickness symptoms were associated with objective or subjective measures of sleep. Rhinitis, but not conjunctivitis, was correlated to worse subjective sleep and more slow wave sleep in allergy. Functional status, but not disease activity, predicted lower subjective sleep in RA. Conclusion: This study tentatively indicates that both patients with allergy and RA display sleep alterations but does not support inflammation as an independent predictor of the sleep disturbance across these patient groups

Evidence of fatigue, disordered sleep and peripheral inflammation, but not increased brain TSPO expression, in seasonal allergy : A [11C]PBR28 PET study

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-11]PBR28. In addition, TNF-alpha, IL-5, IL-6, IL-8 and IFN-gamma 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-alpha 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