Heidi Ormstad

SUSPENDED PARTICULATE MATTER IN INDOOR AIR: ADJUVANTS AND ALLERGEN CARRIERS

The overall purpose of this study was to investigate how airborne house dust particles may contribute to an allergic immune response, and thereby also to asthma and other respiratory symptoms. The following aims were set: first, to quantify and characterize indoor suspended particulate matter (SPM) with regard to amount, as well as elemental and size distribution, second, to identify possible mechanisms by which SPM may affect the allergic immune response. A vast majority of the particles in SPM samples from homes in Oslo were found to be less than 2.5 microm in diameter. This PM(2.5) fraction contained, in addition to a large amount of sulfur aerosols and silicates, a lot of soot particles. Most of these were less than 1 microm in diameter. Using an immunogold labeling technique, we found that these soot particles carried cat, dog and birch allergens on their surface. These results show that indoor SPM contains a lot of potential allergen carriers, i.e. soot particles (carbon aggregates), most of them less that 1 microm in diameter and therefore able to transport allergens deep into the respiratory tree. We further found that diesel exhaust particles (DEP), which is likely the main soot component of SPM, adsorbed several well-known allergens in vitro. Furthermore, SPM was found to elicit a local lymph node inflammatory response, and to have an adjuvant activity on the production of IgE antibodies to ovalbumin (OA).

Airborne house dust elicits a local lymph node reaction and has an adjuvant effect on specific IgE production in the mouse

Indoor suspended particulate matter (SPM) consists of many different types of particles, the vast majority of which are less than 2.5 microm in diameter. An important question is how these particles, being inhalable, contribute to asthma and respiratory symptoms. One possibility is that these particles have an adjuvant effect on the immune response and increase the IgE production, or cause a non-specific irritation in the airways, contributing to bronchial hyper-responsiveness. In this study, the adjuvant activity of indoor SPM on the response to the model allergen ovalbumin (OA) in BALB/c mice was investigated, using the popliteal lymph node (PLN) assay. The adjuvant activity on the local lymph node response was determined by measuring the PLN weight, cell numbers and cell proliferation, and the adjuvant activity on the IgE production by measuring the levels of serum IgE specific to OA. SPM was found to give a significant PLN response, both when injected alone and together with OA. SPM was also found to enhance the production of specific IgE to OA when injected together with OA, after reinjection with OA, compared with immunisation with OA alone.

The fungal cell wall component β-1,3-glucan has an adjuvant effect on the allergic response to ovalbumin in mice.

The polyglucose beta-1,3-D-glucan is a major structural component of the cell wall of yeasts and fungi. In the present study, the adjuvant activity of beta-1,3-glucan from the fungus Sclerotinia sclerotiorum (SSG) on the response to the model allergen ovalbumin (OA) was studied, using the popliteal lymph node assay (PLNA) in BALB/c mice. The adjuvant activity on the local cellular response was determined by measuring the weight, cell number, and proliferation of the extracted PLNs. The levels of OA-specific immunoglobulin (Ig)E, IgG1, and IgG2a in serum were measured by enzyme-linked immunosorbent assay (ELISA). Groups of 8 mice were given either SSG + OA, SSG alone, or OA alone on d 0. Thereafter they were exsanguinated on d 20, or reinjected with OA on d 21, before exsanguination on d 26 or 33. Only on d 26 was SSG + OA found to significantly increase the PLN weight and cell numbers, but not cell proliferation (thymidine incorporation), compared with OA or SSG alone. SSG + OA was also found to significantly increase both the anti-OA IgE and IgG1 levels on d 20, 26, and 33 compared to OA alone. Compared to SSG alone, SSG + OA increased the OA-specific IgE and IgG 1 levels significantly on d 26 and 33, but not on d 20. A similar increase was not found for IgG2a. Our results show that beta-1,3-D-glucan provides a clear Th2-dependent (allergic) immune response to OA, indicated by elevated levels of IgE and IgG1 and not IgG2a, in the mouse model used.

Mould extracts increase the allergic response to ovalbumin in mice

Background Exposure to moulds in indoor air is thought to induce asthma in susceptible persons. Moulds may contain several potent allergens. However, more importantly, moulds may increase the allergic response to other allergens (adjuvant effect). Previously, we have found that a β‐1,3‐glucan from the cell wall of the fungus Sclerotinia sclerotiorum increases the allergic response to the model allergen ovalbumin (OVA) in a mouse model.

The effect of endotoxin on the production of IgE, IgG1 and IgG2a antibodies against the cat allergen Fel d 1 in mice

BACKGROUND Endotoxin/LPS is ubiquitous in our environment. The question whether lipopolysaccharide (LPS) is beneficial or disease-promoting in relation to asthma and allergy has been raised in several recent studies. Some have reported a positive correlation between the level of LPS in house dust and the symptoms of asthmatic children. Others have found that exposure to LPS appears to protect against the development of atopic disease in children. OBJECTIVES We performed a study in mice to examine the antibody response after subcutaneous immunization with LPS and the cat allergen Fel d 1. We asked whether LPS would increase the response and direct the antibody production towards an allergic (IgE), or non-allergic (IgG2a) antibody profile. In rodents both IgE and IgG1 are antibodies produced under Th2-dependence and IgG2a antibodies under Th1-dependence. Also, when LPS and Fel d 1 are introduced to the immune system, we asked whether the timing of the two agents relative to each other is crucial. METHODS The mice were injected subcutaneously with LPS and/or Fel d 1 four times in various orders. IgE, IgG1 and IgG2a antibodies specific to Fel d 1 were measured in serum using ELISA. RESULTS A strong antibody response, both for IgE, IgG1 and IgG2a, was observed only when Fel d 1 and LPS were injected simultaneously, and in particular after repeated injections. CONCLUSION A strong specific antibody response was observed, both for IgE, IgG1 and IgG2a, only when LPS was introduced to the immune system together with the cat allergen Fel d 1. No such adjuvant effect was observed when LPS was introduced alone prior to or subsequent to the allergen. The resulting antibody response was not polarized in terms of Th1- or Th2-dependence.

Scanning electron microscopy of immunogold labeled cat allergens (Fel d 1) on the surface of airborne house dust particles.

This study investigated the ability of an immunogold labeling technique to demonstrate the presence of Fel d 1 (domestic cat) allergens on the surface of particles in samples of airborne house dust. Suspended particulate matter was sampled from ten Norwegian households, five with and five without a domestic cat. The specimens were immunogold labeled and examined in the backscatter electron imaging mode of the scanning electron microscope and in the transmission electron microscope. X-ray microanalysis was also applied to execute element analysis of the suspended particular matter. The gold probe was mainly detected on carbon particles in the suspended particulate matter, both on small (< 1 microns) and larger carbon aggregates (1-10 microns). The present method may be useful in studying the localisation of different allergens on airborne house dust particles of various sizes and composition.

Recovery from major depressive disorder episode after non‐pharmacological treatment is associated with normalized cytokine levels

Several lines of evidence show that the immune system is implicated in the pathophysiology of major depressive disorder (MDD) and that treatment with antidepressants affects cytokine and C‐reactive protein (CRP) levels. Few studies have investigated immune markers during non‐pharmacological treatment. In this follow‐up study, we investigated whether CRP and elevated plasma cytokine levels observed before treatment of an acute episode of MDD are normalized during non‐pharmacological treatment.

Serum Levels of Cytokines, Glucose, and Hemoglobin as Possible Predictors of Poststroke Depression, and Association With Poststroke Fatigue

ABSTRACT Depression is a frequent and potentially disabling sequela of stroke. In the present study, we investigated the ability of stroke type, infarct volume, and laterality, and the levels of various cytokines and other blood components in the acute phase of acute ischemic stroke (AIS) in 45 patients, to predict the level of depression (Beck Depression Inventory [BDI] score) at 6, 12, and 18 months after its onset. The BDI score at 12 months poststroke was positively correlated with the acute serum level of glucose (r = 0.32, p = .038). When excluding the patients using antidepressants, the correlation between glucose level and later depression became significant at all three time points. A general association was found between depression and fatigue. Novel findings are that high acute serum levels of glucose may predict depression after AIS, a glucose level of approximately 126 mg/dL at admission might be a critical limit. Furthermore, depression and fatigue are two generally related—although independent—sequelae of stroke. Our findings did not support a causal immunological etiology for poststroke depression (PSD), as has been suggested previously for poststroke fatigue (PSF) in the same study sample.

Age, education and dementia related deaths. The Norwegian Counties Study and The Cohort of Norway

An inverse relationship between educational level and dementia has been reported in several studies. In this study we investigated the relationship between educational level and dementia related deaths for cohorts of people all born during 1915-39. The cohorts were followed up from adulthood or old age, taking into account possible confounders and mediating paths. Our study population comprised participants in Norwegian health examination studies in the period 1974-2002; The Counties Study and Cohort of Norway (CONOR). Dementia related deaths were defined as deaths with a dementia diagnosis on the death certificate and linked using the Cause of Death Registry to year 2012. The study included 90,843 participants, 2.06 million person years and 2440 dementia related deaths. Cox regression was used to assess the association between education and dementia related deaths. Both high and middle educational levels were associated with lower dementia related death risk compared to those with low education when follow-up started in adulthood (35-49 years, high versus low education: HR=0.68, 95% confidence interval (CI) 0.50-0.93; 50-69 years, high versus low education: HR=0.52, 95% CI 0.34-0.80). However, when follow-up started at old age (70-80 years) there was no significant association between education and dementia related death. Restricting the study population to those born during a five-year period 1925-29 (the birth cohort overlapping all three age groups), gave similar main findings. The protective effects found for both high and middle educational level compared to low education were robust to adjustment for cardiovascular health and life style factors, suggesting education to be a protective factor for dementia related death. Both high and middle educational levels were associated with decreased dementia related death risk compared with low educational level when follow-up started in adulthood, but no association was observed when follow-up started at old age.

Inflammation-Induced Catabolism of Tryptophan and Tyrosine in Acute Ischemic Stroke

Whether the inflammatory response that accompanies acute ischemic stroke induces the kynurenine pathway is currently a matter of conjecture. Activation of this pathway may disturb active metabolites. The aim of this study was thus to characterize the catabolism of tryptophan and tyrosine in acute ischemic stroke (AIS) patients, and its association with cytokines, C-reactive protein, and glucose. Serum levels of 5-hydroxytryptamine, tryptophan catabolites, and competing amino acids and significant ratios of these were measured in 45 AIS patients and compared to those of 40 control subjects. Furthermore, associations between the serum levels of these biomarkers and serum levels of cytokines, C-reactive protein, and glucose were determined. Significantly lower levels of tryptophan and tyrosine in the stroke group indicate increased tryptophan and tyrosine oxidation in acute ischemic stroke, while significantly lowered tryptophan index and tyrosine index indicate a reduced capacity for the synthesis of 5-hydroxytryptamine and catecholamines in the brain, respectively. Furthermore, our findings indicate that the proinflammatory response in acute ischemic stroke may be responsible for a reduced capacity for the biosynthesis of brain catecholamines and mediate neurotoxic effects. Meanwhile, the anti-inflammatory IL-10 may exert a neuroprotective effect and prevent the putative reduced capacity for 5-hydroxytryptamine synthesis in the brain. These mechanisms may be involved in several sequelae following stroke, such as cognitive impairment, depression, and fatigue.