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

BACKGROUND: 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. METHODS: We obtained clinical assessments and blood for CRP and cytokine analysis from 50 unmedicated MDD patients, and cytokine levels from healthy controls. The patients received 'therapy as usual' for 12 weeks, and the assessments were then repeated. Of the 43 completers, 29 patients did not receive medication. RESULTS: In the patients receiving treatment without antidepressants, the depressive symptoms and the plasma levels of eight cytokines (interleukin (IL)-1Ra, IL-5,-6,-8,-10, G-CSF, IFN-γ, and TNF-α) were significantly reduced (P = 0.002-0.048). The cytokine levels were no longer different from the controls. The plasma CRP level did not change. CONCLUSION: Cytokine plasma levels normalized during recovery from an acute depressive episode in MDD without antidepressant treatment. These findings may have implications for the understanding of the role of the immune system in depression and recovery from depression.

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 beta-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. OBJECTIVE: In the present study, we wanted to confirm the adjuvant effect of another beta-1,3-glucan, MacroGard (MG) from baker's yeast in this model. More importantly, we wished to explore the putative effects of extracts from the moulds Cladosporium herbarum (CH) and Penicillium chrysogenum (PC) using the very same model as used to explore effects of beta-glucans. METHODS: Groups of eight Balb/c mice were injected with OVA alone, OVA+extract or OVA+MG, into one footpad. On day 21, all mice were reinjected with OVA, before exsanguination on day 26. The levels of OVA-specific IgE, IgG1 and IgG2a in serum were measured by ELISA. RESULTS: Compared with OVA alone, OVA+MG, OVA+CH extract and OVA+PC extract increased OVA-specific IgE and IgG1 levels significantly. For all groups, the levels of IgG2a anti-OVA remained similar to those of the OVA-alone group. CONCLUSIONS: Our results show that extracts from CH and PC, and the beta-1,3/1,6-glucan from baker's yeast have adjuvant effects on the allergic response in mice.

[Airborne dust particles in indoor environment and allergy]. / Svevestøvspartikler i innemiljøet og allergi.

BACKGROUND: The overall aim of this study was to investigate how airborne house dust particles may contribute to an allergic immune response, and thereby also to asthma and allergic diseases. MATERIAL AND METHODS: Using transmission electron microscopy, we quantified and characterized airborne house dust particles, with regard to elemental and size distribution. Furthermore, an immunogold labelling technique was used to study whether some common allergens were present on the surface of airborne house dust particles. Finally, a mouse model was used to study the adjuvant activity of airborne house dust on the IgE antibody response. RESULTS: A vast majority of the airborne particles samples from homes in Oslo were found to be less than 2.5 microns in diameter, thus they are liable to penetrate deep into the respiratory tree. This PM2.5 fraction contained, in addition to sulphur aerosols and silicates, many soot particles, most of them being less than 1 micron in diameter. These soot particles were found to carry allergens on their surface. We also found that diesel exhaust particles, which is probably a main soot component of airborne house dust, absorbed several wellknown allergens in vitro. Furthermore, the airborne house dust particles were found to elicit a local lymph node response, and to have an adjuvant activity on the production of IgE antibodies to ovalbumin as a model allergen. INTERPRETATION: These results show that indoor suspended particulate matter contains a lot of potential allergen carriers, i.e. soot particles (carbon aggregates), most of them being less that 1 micron in diameter and thereby able to transport allergens deep into the airways. In addition, our results indicate that suspended particulate matter may have an adjuvant effect on the production of IgE to common environmental allergens, and also may provoke a local inflammatory response.

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).

The fungal cell wall component beta-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.

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.

Human IgE production in hu-PBL-SCID mice injected with birch pollen and diesel exhaust particles.

Mice with severe combined immunodeficiency were transplanted with human peripheral blood lymphocytes (hu-PBL-SCID mice). The response to immunisation with birch pollen was used to study possible effects of diesel exhaust particles (DEP) and aluminium hydroxide (Al(OH)3) on human IgE production in this human in vivo model. The adjuvants were well tolerated, as determined by the number of human cells in the peritoneal cavity at the end of the experiments. Total and birch pollen-specific IgE was detected in 76 and 41% of the mice, respectively. In the present experiments where the mice were stimulated early with birch pollen, a doubling in percentage of hu-PBL-SCID mice with production of specific IgE was observed, as compared to later stimulation used in previous experiments. Although a tendency to higher total IgE levels was observed after treatment with DEP, no statistically significant adjuvant effect of DEP or Al(OH)3 could be demonstrated. Electron microscopy analysis after immunogold labelling showed that the major birch pollen allergen Bet v I was released from the pollen grains and adsorbed to the surface of the DEP. Early stimulation with allergen appears to be important for optimal production of specific IgE in the hu-PBL-SCID model. However, our results show that further improvements are needed in order to demonstrate the expected effects from adjuvants and environmental pollutants.

Airborne house dust particles and diesel exhaust particles as allergen carriers.

BACKGROUND: 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. The question arises how these particles may contribute to asthma and respiratory symptoms. One possibility is that airborne dust particles act as carriers of allergens into the airways, as several allergens have been found to be associated with inhalable airborne dust particles. OBJECTIVE: We studied the presence of three different allergens on the surface of SPM, i.e. Can f 1 (dog), Bet v 1 (birch pollen) and Der p 1 (house dust mite). We also examined the ability of diesel exhaust particulates (DEP) to attach these allergens and Fel d I (cat) in vitro. METHODS: SPM was collected on polycarbonate filters and an immunogold labelling technique was used to detect the allergens on the particles. The specimens were examined in the backscatter mode of a scanning electron microscope. The same technique was used to examine the binding of the allergens to DEP, after exposing DEP to either crude allergen extracts or partly purified allergens. RESULTS: Both Can f 1 and Bet v 1 allergens were detected on the surface of the soot particles in SPM mixtures, although to a lesser degree than previously found with Fel d 1. Der p 1 (house dust mite), however, did not show any significant binding to SPM particles. Furthermore, DEP had the ability to adsorb all four allergens in vitro, although to a varying extent. CONCLUSION: Soot particles in airborne house dust may act as carriers of several allergens in indoor air. Furthermore, DEP has the ability to bind all the four allergens investigated under aqueous conditions in vitro.

Evaporated germanium films as supports for microanalysis of carbon and silicon containing specimens.

A preparation procedure is described for producing specimen supports of evaporated germanium. The germanium film is used as a replacement for films of carbon and silicon when microanalytical techniques like energy dispersive X-ray microanalysis (XRMA) or electron energy loss spectroscopy (EELS) are focusing on particulates containing these elements. The supports can be produced with high reproducibility within a thickness range of 15 to 30 nm and of a quality suitable also for high resolution transmission electron microscopy.

Quantification and characterisation of suspended particulate matter in indoor air.

Quantification and characterisation of suspended particulate matter (SPM) from homes in the city of Oslo was carried out. In 29 households the dust concentrations were found to vary between 9 and 56 mug/m(3) (median value 26 mug/m (3)). In 12 of the 29 households, a thorough analysis was carried out to determine the size and element distribution of the particles using transmission electron microscopy (TEM) and X-ray microanalysis (XRMA). The vast majority of the collected particles were less than 2.5 mum in diameter, i.e. they belonged to the fine fraction. In this fraction a considerable amount of soot and sulphur particles were found, usually less than 1 mum in diameter. The coarse fraction (particles > 2.5 mum in diameter) was found to consist mainly of organic material, silicates and larger soot aggregates. Both a thorough analysis of individual particles and a "bulk analysis" (i.e. recording XRMA spectra from whole grid masks) were performed, and the two methods were found to show good agreement.

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.