An elevated pro-inflammatory cytokine profile in multiple chemical sensitivity

Elberling, Jesper; Brix, Susanne; Szecsi, Pal B.; Vesterhauge, S.; Skovbjerg, Sine

doi:10.1016/j.psyneuen.2013.11.012

Cited by 39 publications

(36 citation statements)

References 48 publications

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“…These observations are supported by the significant negative correlation found between ADORA2A mRNA and both IFNG and IL4. Our data partially replicated the findings of Dantoft et al [10], that demonstrated higher plasma concentrations of several cytokines including IL-4, but not IFN-γ, in MCS cases than in healthy controls.…”

Section: Discussionsupporting

confidence: 91%

“…In the last decade, literature data provided evidence for the association of MCS with increased oxidative/nitrosative stress and inflammation [9][10][11][12][13][14], likely resulting from defects in xenobiotic metabolism and antioxidant enzyme defenses [26]. A chronic imbalance in redox homeostasis promotes the development of inflammation mainly through the dysregulation of immune response cells and the activation of pro-inflammatory transcription factors [27].…”

Section: Discussionmentioning

confidence: 99%

“…To date the proposed etiopathogenetic mechanism involves an aberrant activation of the vicious cycle N-methyl-d-aspartate (NMDA)-nitric oxide/peroxynitrite triggered by various chemical agents, that ultimately lead to oxidative stress and activation of pro-inflammatory transcription factors [8]. Indeed, dramatically increased levels of reactive oxygen and nitrogen species (ROS, RNS), as well as pro-inflammatory cytokines and the presence of autoimmune antibodies, have been reported in MCS patients compared with healthy subjects [9][10][11][12][13][14]. Moreover, a link has been suggested between MCS and inherited or acquired defects in genes coding for enzymes involved in xenobiotic metabolism phase I and II, antioxidant defense, lipid metabolism and one-carbon pathway [11,12,[15][16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

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The SNP rs2298383 Reduces ADORA2A Gene Transcription and Positively Associates with Cytokine Production by Peripheral Blood Mononuclear Cells in Patients with Multiple Chemical Sensitivity

Cannata¹,

Luca²,

Korkina³

et al. 2020

IJMS

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Systemic inflammation and immune activation are striking features of multiple chemical sensitivity (MCS). The rs2298383 SNP of ADORA2A gene, coding for adenosine receptor type 2A (A2AR), has been involved in aberrant immune activation. Here we aimed to assess the prevalence of this SNP in 279 MCS patients and 238 healthy subjects, and its influence on ADORA2A, IFNG and IL4 transcript amounts in peripheral blood mononuclear cells of randomly selected patients (n = 70) and controls (n = 66) having different ADORA2A genotypes. The ADORA2A rs2298383 TT mutated genotype, significantly more frequent in MCS patients than in controls, was associated with a three-fold increased risk for MCS (O.R. = 2.86; C.I. 95% 1.99-4.12, p < 0.0001), while the CT genotype, highly prevalent among controls, resulted to be protective (O.R. = 0.33; C.I. 95% 0.224-0.475, p < 0.0001). Notably, ADORA2A mRNA levels were significantly lower, while IFNG, but not IL4, mRNA levels were significantly higher in TT MCS patients compared with controls. A significant negative correlation was found between ADORA2A and both IFNG and IL4, while a significant positive correlation was found between IFNG and IL4. These findings suggest that A2AR defective signaling may play a relevant role in PBMC shift towards a pro-inflammatory phenotype in MCS patients.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The SNP rs2298383 Reduces ADORA2A Gene Transcription and Positively Associates with Cytokine Production by Peripheral Blood Mononuclear Cells in Patients with Multiple Chemical Sensitivity

Cannata¹,

Luca²,

Korkina³

et al. 2020

IJMS

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“…After the bioaccumulation of a toxicant burden and the consequent immune dysregulation [36], seemingly insignificant environmental triggers can lead to the release of proinflammatory cytokines [46], antibodies, chemokines, and interleukins and produce a variety of symptoms, including neuropsychiatric issues, in the affected patient [36, 40, 47, 48]. Gluten is one such common trigger, and is hypothesized to be the culprit in the above case report.…”

Section: Discussionmentioning

confidence: 99%

Gluten Sensitivity Presenting as a Neuropsychiatric Disorder

Genuis

Lobo

2014

Gastroenterology Research and Practice

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There has been increasing recognition in the medical community and the general public of the widespread prevalence of gluten sensitivity. Celiac disease (CD) was initially believed to be the sole source of this phenomenon. Signs and symptoms indicative of nonceliac gluten sensitivity (NCGS), in which classical serum and intestinal findings of CD may be absent, have been frequently reported of late. Clinical manifestations in patients with NCGS are characteristically triggered by gluten and are ameliorated or resolved within days to weeks of commencing a gluten-free diet. Emerging scientific literature contains several reports linking gluten sensitivity states with neuropsychiatric manifestations including autism, schizophrenia, and ataxia. A clinical review of gluten sensitivity is presented alongside a case illustrating the life-changing difference achieved by gluten elimination in a patient with a longstanding history of auditory and visual hallucinations. Physicians in clinical practice should routinely consider sensitivity issues as an etiological determinant of otherwise inexplicable symptoms. Pathophysiologic mechanisms to explain the multisystem symptomatology with gluten sensitivity are considered.

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“…Sensitivity to chemicals is a toxicological concept 41 , contained in the dose-response relationship 42 . Sensitivity also includes the concept of hypersensitivity 43 , although controversy surrounds the nature of effects from very low exposures 44 . Research into the possible mechanisms of MCS is far from complete 45 .…”

Section: Discussionmentioning

confidence: 99%

Review of the Available Scientific Evidence on Multiple Chemical Sensitivity Syndrome

2016

ARC Journal of Pharmaceutical Sciences

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Background: Multiple Chemical Sensitivity (MCS) Syndrome poses many faces and it is related to previous exposure to substances found in the environment, at well-tolerated concentration by the general population. There are a lot of sources of exposure and there is no typical clinical pattern, as well as several degrees of severity in the subjects affected by MCS Syndrome. For all these reasons, the MCS Syndrome becomes a complex disease with difficult diagnosis and management. The aim of this study is to review and to update the available scientific evidence on MCS Syndrome. Methodology: A systematic revision of the available evidence has been made, and updated the available evidence. The following sources were used: Medline, Embase, PSYCINFO, Toxline, UpToDate, IBSST, CISDOC, The Cochrane Library and Centre for Reviews and Dissemination (CRD). Two reviewers independently made the selection of recovered articles, applying the inclusion and exclusion criteria for the final selection of studies. There were identified 613 studies of which 27 were selected for the 5 analyzed clinical areas: 1) Epidemiology, 2) Clinical manifestations and co-morbid clinical conditions, 3) Diagnosis of MCS syndrome, 4) Physical, Psychological and Social impact on the Quality of Life 5) Therapeutic and prevention approaches for MCS Syndrome. Results: The estimation of MCS´s prevalence can range between 0.02% and 0.04%, increasing to 19% in people with an added diagnosis of allergy. The most frequently affected systems in the MCS Syndrome are the digestive tract, the cardiovascular one and the skin. Also, the mental sphere is affected with certain frequency. The MCS´s diagnosis can be difficult, due to the variety of symptoms the disease can show from the beginning and because of the wide range of different definitions about the same disease that can be made. The clinical suspicion after a correct anamnesis and physical exam and the use of the Quick Environmental Exposure and Sensitivity Inventory (QEESI), in Spanish version can help with the diagnosis. People affected by MCS Syndrome seems to decrease their quality of life in a significant way, even reaching self-isolation in an attempt to reduce the exposition to trigger substances or due to the serious physical deterioration in case of continuous expositions. The more effective therapeutic intervention consists on avoiding new re-exposure to the leading substances. Conclusions: The MCS is frequently associated with a previous allergic subject. It can affect multiple systems simultaneously, most often the gastrointestinal and cardiovascular systems, the skin and the mental sphere. The non-specific symptoms and the lack of consensus about the definition of MCS deter an early diagnosis of the disease. There is a Spanish version of the QEESI of reference. It is believed that the adoption of measures to sensitize the general population about MCS, could influence the reduction of exposures to trigger substances and improve understanding of this disease and people who suffer it. Actually, the...

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An elevated pro-inflammatory cytokine profile in multiple chemical sensitivity

Cited by 39 publications

References 48 publications

The SNP rs2298383 Reduces ADORA2A Gene Transcription and Positively Associates with Cytokine Production by Peripheral Blood Mononuclear Cells in Patients with Multiple Chemical Sensitivity

The SNP rs2298383 Reduces ADORA2A Gene Transcription and Positively Associates with Cytokine Production by Peripheral Blood Mononuclear Cells in Patients with Multiple Chemical Sensitivity

Gluten Sensitivity Presenting as a Neuropsychiatric Disorder

Review of the Available Scientific Evidence on Multiple Chemical Sensitivity Syndrome

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