Inflammatory Mediator Profiling of n-butanol Exposed Upper Airways in Individuals with Multiple Chemical Sensitivity

PLOS ONE, Dec 2019

Background Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by reports of recurrent symptoms in response to low level exposure to various chemical substances. Recent findings suggests that dysregulation of the immune system may play a role in MCS pathophysiology. Objectives The aim of this study was to examine baseline and low dose n-butanol-induced upper airway inflammatory response profiles in MCS subjects versus healthy controls. Method Eighteen participants with MCS and 18 age- and sex-matched healthy controls were enrolled in the study. Epithelial lining fluid was collected from the nasal cavity at three time points: baseline, within 15 minutes after being exposed to 3.7 ppm n-butanol in an exposure chamber and four hours after exposure termination. A total of 19 cytokines and chemokines were quantified. Furthermore, at baseline and during the exposure session, participants rated the perceived intensity, valence and levels of symptoms and autonomic recordings were obtained. Results The physiological and psychophysical measurements during the n-butanol exposure session verified a specific response in MCS individuals only. However, MCS subjects and healthy controls displayed similar upper airway inflammatory mediator profiles (P>0.05) at baseline. Likewise, direct comparison of mediator levels in the MCS group and controls after n-butanol exposure revealed no significant group differences. Conclusion We demonstrate no abnormal upper airway inflammatory mediator levels in MCS subjects before or after a symptom-eliciting exposure to low dose n-butanol, implying that upper airways of MCS subjects are functionally intact at the level of cytokine and chemokine production and secretory capacity. This suggests that previous findings of increased cytokine plasma levels in MCS are unlikely to be caused by systemic priming via excessive upper airway inflammatory processes.

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Inflammatory Mediator Profiling of n-butanol Exposed Upper Airways in Individuals with Multiple Chemical Sensitivity

November Inflammatory Mediator Profiling of n-butanol Exposed Upper Airways in Individuals with Multiple Chemical Sensitivity Thomas Meinertz Dantoft 0 1 2 Sine Skovbjerg 0 1 2 Linus Andersson 0 1 2 Anna-Sara Claeson 0 1 2 Nina Lind 0 1 2 Steven Nordin 0 1 2 Susanne Brix 0 1 2 0 Editor: Gernot Zissel , Universitatsklinikum Freiburg, GERMANY 1 Current Address: Department of Economics, Swedish University of Agricultural Sciences , Uppsala , Sweden 2 1 Danish Research Centre for Chemical Sensitivities, Copenhagen University Hospital, Gentofte, Denmark, 2 Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark , Kongens Lyngby , Denmark , 3 Research Centre for Prevention and Health , Capital Region, Copenhagen , Denmark , 4 Department of Psychology, Umeå University, Umeå, Sweden, 5 Department of Occupational and Public Health Sciences, University of Gävle , Umeå , Sweden - Eighteen participants with MCS and 18 age- and sex-matched healthy controls were enrolled in the study. Epithelial lining fluid was collected from the nasal cavity at three time points: baseline, within 15 minutes after being exposed to 3.7 ppm n-butanol in an exposure chamber and four hours after exposure termination. A total of 19 cytokines and chemokines were quantified. Furthermore, at baseline and during the exposure session, participants rated the perceived intensity, valence and levels of symptoms and autonomic recordings were obtained. Results The physiological and psychophysical measurements during the n-butanol exposure ses sion verified a specific response in MCS individuals only. However, MCS subjects and healthy controls displayed similar upper airway inflammatory mediator profiles (P>0.05) at Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by reports of recurrent symptoms in response to low level exposure to various chemical substances. Recent findings suggests that dysregulation of the immune system may play a role in MCS pathophysiology. The aim of this study was to examine baseline and low dose n-butanol-induced upper air way inflammatory response profiles in MCS subjects versus healthy controls. OPEN ACCESS Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This work was supported by the Swedish Research Council for Health, Working Life and Welfare (2011-0396) (http://www.forte.se/en/, SN); the Swedish Research Council Formas (http://www.vr.se/ inenglish.4.12fff4451215cbd83e4800015152.html, AC); the Danish Ministry of the Environment (http:// eng.mim.dk/, sponsored the Danish Research Centre for Chemical Sensitivities). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Background Objectives Method Competing Interests: The authors have declared that no competing interests exist. baseline. Likewise, direct comparison of mediator levels in the MCS group and controls after n-butanol exposure revealed no significant group differences. Conclusion We demonstrate no abnormal upper airway inflammatory mediator levels in MCS subjects before or after a symptom-eliciting exposure to low dose n-butanol, implying that upper airways of MCS subjects are functionally intact at the level of cytokine and chemokine production and secretory capacity. This suggests that previous findings of increased cytokine plasma levels in MCS are unlikely to be caused by systemic priming via excessive upper airway inflammatory processes. Introduction A substantial proportion of the adult population report different degrees of chemical intolerances towards everyday chemicals, e.g. fragranced consumer products, car exhaust, pesticides and new furniture’s at concentrations usually considered to be harmless [ 1 ]. The estimated prevalence varies substantially but in about 0.5% to 6.3% of the population [ 2–4,4–8 ], exposures to everyday chemicals elicit a complex array of symptoms at a much greater magnitude and often with disabling consequences in the form of social and occupational lifestyle changes and reduction in life quality [ 9,10 ]. Multiple chemical sensitivity (MCS) is a common term used to describe this severe form of chemical intolerance [ 11,12 ]. Controversially, no dose-response relationship has been identified linking exposure concentration to the symptom magnitude in MCS [ 13 ] and the type and severity of reported symptoms to an exposure are highly variable. Symptoms from the central nervous system (CNS) conveyed by migraine headaches, dizziness, extreme fatigue, and concentration difficulties are common, often combined with non-specific symptoms from other organ systems such as the mucosa/respiratory tract, musculoskeletal system and/or the gastro-intestinal tract [ 8,11,13 ]. Both physiological and psychological processes have been suggested as underlying mechanisms in MCS, but no definit con (...truncated)


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Thomas Meinertz Dantoft, Sine Skovbjerg, Linus Andersson, Anna-Sara Claeson, Nina Lind, Steven Nordin, Susanne Brix. Inflammatory Mediator Profiling of n-butanol Exposed Upper Airways in Individuals with Multiple Chemical Sensitivity, PLOS ONE, 2015, 11, DOI: 10.1371/journal.pone.0143534