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Biomedical subjects

M Løvik

Publications and source records attributed to M Løvik.

At least 19 recordsLinked to original sources
PubMed2006

Mycotoxin-induced depletion of intracellular glutathione and altered cytokine production in the human alveolar epithelial cell line A549.

Mould exposure has been associated with asthma and other inflammatory airway conditions. However, cellular effects of inhaled mould components are not well understood. We hypothesised that host defence mechanisms, such as production of cytokines (TGFbeta1, IL-6 and IL-8) and the intracellular antioxidant glutathione (GSH), could be adversely affected by different concentrations of mycotoxins. We studied the effects of citrinin and gliotoxin on lipopolysaccharide (LPS)-stimulated alveolar epithelial cells (A549). Cytokines in cell culture supernatants were analysed by ELISA and levels of GSH were measured by colorimetric (absorbance) determination. We found that GSH decreased in a dose- and time-dependent manner when cells were exposed to citrinin in particular. TGFbeta1 was moderately reduced at low mycotoxin concentrations but elevated at higher sub-toxic concentrations. A tendency for an inverse relationship between TGFbeta1 and GSH levels was observed. IL-6 and IL-8 were not significantly reduced at non-toxic mycotoxin concentrations. Thus, reduced epithelial GSH and TGFbeta1 levels combined with elevated IL-6 and IL-8 levels may result in increased pro-inflammatory activity during mycotoxin exposure. We suggest that this mechanism can contribute to inflammation in mould exposure.

Cell Line↗
PubMed2006

Asthma in every fifth child in Oslo, Norway: a 10-year follow up of a birth cohort study.

BACKGROUND: The western world's increase in childhood asthma is suggested to level off. We aimed to investigate asthma prevalence in 10-year-old children within the prospective birth cohort Environment and Childhood Asthma (ECA) Study in Oslo established in 1992/1993. SUBJECTS AND METHODS: Six hundred and sixteen (77%) of 803 children (mean age 10.9 +/- 0.9 (SD) years) with lung function measurements at birth were reinvestigated at age 10 years. At birth they corresponded to the entire birth cohort (n = 3754) regarding gender, socio-demographic factors, parental allergic diseases, pet keeping and maternal smoking. Results from structured parental interview, spirometry, and skin prick test for inhalant and food allergens are presented. Asthma definition required minimum two positive criteria, (i) doctor's diagnosis of asthma, (ii) wheeze and/or chest tightness, (iii) use of anti-asthmatic treatment. Current asthma required asthma definition plus either (ii) and/or (iii) in the last 12 months, and/or > or = 10% fall in forced expired volume in 1 s after treadmill running. RESULTS: Lifetime prevalence of asthma was 20.2%; current asthma 11.1%, doctor diagnosis of asthma 16.1% and wheezes ever 30.3%. Allergic sensitization (29.3% overall) was more common among children with current (56.3%) compared to asymptomatic (last 12 months) (26.0%) or no asthma (27.6%) (P < 0.001). Boys more often than girls had current asthma (14.4 vs 7.1%, P = 0.004), wheeze ever (36.9 vs 22.5%, P = 0.002) and allergic sensitization (36.2 vs 22.1%, respectively, P < 0.001). CONCLUSION: Childhood asthma apparently continues to increase in Oslo, having affected every fifth 10-year-old child.

Asthma↗
PubMed2006

Soluble CD14 at 2 yr of age: gender-related effects of tobacco smoke exposure, recurrent infections and atopic diseases.

The endotoxin receptor soluble CD14 (sCD14) has been implicated in the 'hygiene hypothesis' suggesting reduced allergic sensitization with bacterial stimulation. However, the relationship between early life sCD14 and allergic diseases is conflicting. We aimed to investigate whether possible risk factors for allergic diseases were associated with sCD14 levels at 2 yr of age. In the nested case-control study of the birth cohort studies 'Environment and Childhood Asthma study in Oslo' 411 children selected with recurrent bronchial obstruction (rBO) (n=241) and no bronchial obstruction (n=170) by 2 yr were investigated with skin prick test and structured parental interview at age 2 yr. Exposure to tobacco smoke, pets and infections was recorded semi-annually by questionnaires (0-2 yr). The sCD14 was analysed from frozen, stored serum by ELISA technique. Regression analyses were performed in all subjects with complete data (n=406, 180 girls), and in girls and in boys separately. Mean sCD14 (ng/ml) was significantly higher among girls 2035 (1973-2096) vs. 1947 (1890-2004) (boys). The sCD14 was significantly reduced among girls exposed to antenatal maternal smoking and with parental asthma, after adjusting for age, parental rhino-conjunctivitis, pet keeping and childhood infections. Recurrent otitis media (OM) increased and common colds significantly decreased sCD14 levels in girls. Boys with atopic dermatitis and rBO had reduced sCD14. Pet exposure was not significantly associated with sCD14. We report novel gender-related effects of sCD14 in early life and suggest that gender, tobacco smoke exposure, age and middle ear disease in particular should be accounted for when assessing the role of sCD14 in childhood allergic diseases.

Age Factors↗
PubMed2005

The mycotoxins citrinin and gliotoxin differentially affect production of the pro-inflammatory cytokines tumour necrosis factor-alpha and interleukin-6, and the anti-inflammatory cytokine interleukin-10.

BACKGROUND: Microbial growth is considered one of the major causes of indoor air problems. Moulds have been associated with asthma, allergy and a wide range of diffuse indoor air-related symptoms. However, mechanisms of the adverse health effects are not well understood. OBJECTIVE: We hypothesized that the mycotoxins citrinin and gliotoxin could cause an imbalance between the secretion of the pro-inflammatory cytokines TNF-alpha and IL-6 and the anti-inflammatory cytokine IL-10. METHODS: We investigated the influence of citrinin and gliotoxin on the human monocytic cell line Mono-Mac-6 (MM6) with and without lipopolysaccharide -stimulation. The levels of IL-10, IL-6 and TNF-alpha were analysed in cell culture supernatants by ELISA. Cell viability and cell apoptosis were measured by flow cytometry. RESULTS: The strongest inhibition of cytokine secretion was found for IL-10. IL-6 levels were found to decrease in a dose-dependent manner along with reduced cell viability. TNF-alpha levels increased with low gliotoxin exposure (less than 100 ng/mL), but decreased significantly at 375 ng/mL and higher along with increased cell apoptosis and reduced cell viability. TNF-alpha levels were not reduced by citrinin exposure. CONCLUSION: We observed a cytokine imbalance with a more pronounced reduction of IL-10 concentrations compared with those of TNF-alpha and IL-6. We suggest that low exposure doses of citrinin and gliotoxin (corresponding to less than 100 ng/mL gliotoxin and less than 10 mug/mL citrinin) may inhibit IL-10 and lead to increased risk of an inflammatory response with relative overproduction of TNF-alpha and IL-6. The findings and their clinical implications must be verified by human studies. However, we speculate that the observed biological effects may be of importance as they may partly explain the occurrence of diffuse general indoor air-related symptoms as well as the worsening of asthmatic inflammatory reactions experienced in mouldy environments.

Air Pollution, Indoor↗
PubMed2005

Allergens and endotoxin in settled dust from day-care centers and schools in Oslo, Norway.

UNLABELLED: Allergy to indoor allergens can cause frequent and severe health problems in children. Because little is known about the content of allergens in the indoor environments in Norway, we wanted to assess the levels of cat, dog and mite allergens in schools and day-care centers in Oslo. Allergen levels in dust samples from 155 classrooms and 81 day-care units were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Additionally, we measured the levels of endotoxin in 31 day-care units, using the limulus amebocyte lysate test. Most of the dust samples contained detectable amounts of cat and dog allergens. In mattress and floor dust (day-care centers), and curtain and floor dust (schools) the median Fel d 1 levels were 0.17, 0.002, 0.02 and 0.079 microg/m2, while the median Can f 1 levels were 1.7, 0.03, 0.1 and 0.69 microg/m2, respectively. Levels of cat and dog allergens in school floor dust were associated with the number of pupils with animals at home. In contrast, <1% of the samples had measurable levels of the mite allergen Der p 1. Moreover, the levels of endotoxin tended to be higher in dust from floors (1.4 ng/m2) compared with that from mattresses (0.9 ng/m2). PRACTICAL IMPLICATIONS: To reduce allergen exposure, allergic individuals should be placed in the classes/rooms with the fewest pet owners. Moreover, mattresses in day-care centers are major reservoirs of cat and dog allergens and should be cleaned frequently.

Air Pollution, Indoor↗
PubMed2003

'EUROPART'. Airborne particles in the indoor environment. A European interdisciplinary review of scientific evidence on associations between exposure to particles in buildings and health effects.

The relevance of particle mass, surface area or number concentration as risk indicators for health effects in non-industrial buildings has been assessed by a European interdisciplinary group of researchers (called EUROPART) by reviewing papers identified in Medline, Toxline, and OSH. Studies dealing with dermal effects or cancer or specifically addressing environmental tobacco smoke, house dust-mite, cockroach or animal allergens, microorganisms and pesticides were excluded. A total of 70 papers were reviewed, and eight were identified for the final review: Five experimental studies involving mainly healthy subjects, two cross-sectional office studies and one longitudinal study among elderly on cardiovascular effects. From most studies, no definite conclusions could be drawn. Overall, the group concluded that there is inadequate scientific evidence that airborne, indoor particulate mass or number concentrations can be used as generally applicable risk indicators of health effects in non-industrial buildings and consequently that there is inadequate scientific evidence for establishing limit values or guidelines for particulate mass or number concentrations.

Air Pollution, Indoor↗
PubMed2002

Maternal allergen immunization during pregnancy in a mouse model reduces adult allergy-related antibody responses in the offspring.

BACKGROUND: The immune status and allergen exposure of the mother may influence the immune response in the offspring after birth. This relationship may be important both for allergen avoidance strategies and, alternatively, for allergy prophylaxis by allergen exposure of the mother. OBJECTIVE: The aim of the present study was to investigate the effect of allergen immunization of the mother during pregnancy and postpartum, in relation to the allergy-related immune response (IgE) and the non-allergy-related (IgG2a) response in the offspring. METHODS: Pregnant NIH/OlaHsd females were immunized three times during pregnancy and one time postpartum with ovalbumin and the adjuvant Al(OH)3, and the offspring's ovalbumin-specific IgE, IgG1 and IgG2a responses were measured after challenge with the same allergen as young adults. Ovalbumin-specific IgE, IgG1 and IgG2a responses were also analysed in offspring of NIH/OlaHsd females immunized once at different times during pregnancy: about 3 days into pregnancy, mid-pregnancy (10 days into pregnancy) and about 4 days before giving birth (17 days into pregnancy). RESULTS: Allergen immunization of mother during pregnancy and postpartum significantly reduced the IgE response in the progenies, whereas the IgG2a response to the same allergen was increased. Allergen immunization of the mother 3 days into pregnancy resulted in a significantly lower IgE response in offspring compared with the response in offspring of non-immunized mothers and in offspring of mothers immunized 17 days into pregnancy. CONCLUSIONS: Maternal allergen immunization might favour selection for an allergen-specific Th1-dependent antibody response in the offspring. Our results indicate that IgE suppression is stronger after maternal allergen exposure during early pregnancy than after exposure in late pregnancy.

Adjuvants, Immunologic↗
PubMed2001

IgE adjuvant effect caused by particles - immediate and delayed effects.

Diesel exhaust particles are reported to increase the specific IgE response to ovalbumin (OVA) and pollen. Evidence has been provided that the particle core contributes to this adjuvant activity. The purpose of our study was to investigate the effect of well-defined simple particles, polystyrene particles (PSP), on the production of allergen-specific IgE in a mouse model. The IgE adjuvant effect of PSP was investigated in experiments using intranasal (i.n.) instillation, intratracheal (i.t.) instillation or intraperitoneal (i.p.) injection. Delayed and cumulative adjuvant effects were investigated by giving mice i.p. injections with PSP 1-3 days, or on 4 consecutive days before OVA, respectively. The levels of allergen-specific and total IgE were measured. Irrespectively of immunisation route and protocol, OVA in combination with PSP elicited increased levels of both allergen-specific and total IgE when compared with OVA alone. Therefore, in the experimental model, particles were found to augment the specific IgE response to an allergen even when the allergen was introduced several days after the particles. These findings imply that individuals exposed to particulate air pollution at one point of time may develop an increased reaction towards allergens inhaled later that day or even several days after the particle exposure.

Adjuvants, Immunologic↗
PubMed2001

Leptin does not influence the IgE response to ovalbumin in mice.

Leptin is important for maintenance of the body's energy homeostasis and it also increases Th1 and suppresses Th2 cytokine production. We have investigated the effect of leptin on the allergic immune response to the model allergen ovalbumin (OA) by using the popliteal lymph node assay (PLNA) and serum antibody determination in mice. Mice were injected with either leptin i.v. plus OA in one hind footpad, or leptin or OA alone. A booster dose of leptin was given twice and of OA once and the animals were exsanguinated on experimental day 19 when the PLNs also were removed. End-point measurements were serum levels of IgE, IgG1, and IgG2a anti-OA and weight and cell number of the excised PLNs. Leptin given i.v. with the protocol employed altered neither the cellular PLN response nor the specific serum IgE, IgG1, or IgG2a anti-OA levels compared with the group given OA without leptin. Our data indicate that systemic administration of leptin neither suppresses nor enhances the Th2-dependent antibody responses in the present mouse model.

Allergens↗
PubMed2001

Mycobacterium leprae and Mycobacterium lepraemurium infections in domestic and wild animals.

Mycobacterium leprae, the aetiological agent of leprosy in humans, gives rise to a chronic granulomatous disease that affects primarily the skin and peripheral nerves, and secondarily some internal organs such as the testis and the eye; viscera are seldom involved. Depending on host resistance, leprosy may present as a benign disease (tuberculoid leprosy) or as a malignant disease (lepromatous leprosy), with a spectrum of intermediate stages appearing between the two. Immunity against leprosy depends on the cell-mediated immunity of the host, and this is severely compromised in the malignant (lepromatous) form of leprosy. Although culture of M. leprae has never been achieved in artificial media, the bacterium may be grown in several experimental animals, including the armadillo, non-human primates, and to a certain extent, rodents. Naturally acquired leprosy has been reported in wild nine-banded armadillos (Dasypus novemcinctus) and in three species of non-human primates (chimpanzees [Pan troglodytes], sooty mangabey monkeys [Cercocebus atys] and cynomolgus macaques [Macaca fascicularis]), thus qualifying leprosy as a zoonosis. Murine leprosy is a leprosy-like disease of rats and mice, caused by Mycobacterium lepraemurium. The disease affects primarily viscera and the skin, and very rarely peripheral nerves. Depending on the host strain, rodent leprosy may also evolve as 'lepromatous' or 'tuberculoid' leprosy, and strains of mouse that develop intermediate forms of the disease may exist. Growth of M. lepraemurium on conventional media for mycobacteria is not successful, but the bacterium has been cultured on an egg yolk-based medium. Naturally acquired murine leprosy has been observed in rats, mice and cats, but not in humans or any other species. Thus, in contrast to human leprosy, murine leprosy is not a zoonosis.

Animals↗
PubMed2000

[Increased occurrence of allergy--is modern life style the cause?].

BACKGROUND: There is strong evidence that an increase in the occurrence of allergic diseases has taken place in industrialised countries over the last decades. The causes of this increase are unknown, but it seems to be linked to affluence and a modern, "westernized" lifestyle. MATERIAL AND METHODS: Three international research papers are reviewed and discussed in the context of current knowledge of immunoregulatory effects from microbial and allergen exposure. RESULTS: A German report indicates that early attendance (before one year of age) at daycare centres reduced the risk for allergy development in children from small, but not from large families. A Swiss and a Swedish paper report that children of farmers, or students attending anthroposophic Steiner schools had less allergic manifestations than their peers in the same local communities. INTERPRETATION: The findings suggest that groups practising a somewhat simple, "old-fashioned" lifestyle within a modern community have a reduced risk of developing allergic diseases. Proper microbial stimulation of the immune system, possibly via the bacterial flora on the mucosal surfaces of the upper airways and the gut, may act to reduce the risk of becoming allergic. Insufficient microbial stimulation of the immune system may be a "deficiency disease" of modern society, leading to allergy.

Adolescent↗
PubMed2000

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.

Adjuvants, Immunologic↗
PubMed2000

Protective effect of Plantago major L. Pectin polysaccharide against systemic Streptococcus pneumoniae infection in mice.

The antibacterial effect of a soluble pectin polysaccharide, PMII, isolated from the leaves of Plantago major, was examined in inbred NIH/OlaHsd and Fox Chase SCID mice experimentally infected with Streptococcus pneumoniae serotype 6B. Serotype 6B is known to give a more protracted infection when injected intraperitoneally into susceptible mice than more virulent serotypes like type 4. PMII was administered i.p. either once 3 days before challenge or once to thrice from 3 to 48 h after challenge. The number of bacteria in blood and the mouse survival rate were recorded. Pre-challenge administration of PMII and also lipopolysaccharide (LPS), included as a control, gave a dose-dependent protective effect against S. pneumoniae type 6B infection. However, injection of PMII after establishment of the infection in NIH/OlaHsd mice had no effect. The data demonstrate that, firstly, the polysaccharide fraction PMII from P. major protects against pneumococcal infection in mice when administered systemically prechallenge, and secondly that the protective effect is owing to stimulation of the innate and not the adaptive immune system.

Animals↗
PubMed2000

The adjuvant effect of particles-importance of genetic background and pre-sensitisation.

BACKGROUND: We have previously reported that simple and well-characterised particles, such as polystyrene particles (PSP), have an IgE adjuvant effect in mice. The purpose of this study was to explore the importance of genetic background concerning the adjuvant effect of PSP in different strains of mice. METHODS: Inbred NIH/Ola, BALB/c and C3H/HeJ mice were given two intraperitoneal injections with either PSP plus OVA or OVA alone, and then an intraperitoneal challenge with OVA alone. NIH/Ola mice were also pre-sensitised to develop a weak or strong IgE response to OVA, and then given an intraperitoneal challenge with PSP plus OVA or OVA alone. Serum levels of total and allergen-specific IgE and IgG2a were measured. RESULTS: PSP had a specific IgE and IgG2a adjuvant effect in NIH/Ola mice but not in C3H/HeJ and BALB/c mice. Weakly pre-sensitised NIH/Ola mice showed the same response pattern as the naive NIH/Ola mice. In contrast, strongly pre-sensitised mice showed an antibody response pattern similar to that of high-responder BALB/c mice. CONCLUSIONS: Our results indicate that the allergen responder status, either genetic or induced, is of importance for the adjuvant effect from particles. The IgE and IgG2a adjuvant effect may depend on the genetically determined susceptibility of an individual to be influenced by exposure to the adjuvant. Therefore, the allergy-enhancing effect from particle pollution may differ between individuals.

Adjuvants, Immunologic↗
PubMed1999

Interleukin-13 and human immunoglobulin E production in severe combined immunodeficiency mice transplanted with human peripheral blood lymphocytes.

As normal mice do not respond to interleukin-13 (IL-13), we have used mice with severe combined immunodeficiency transplanted with human peripheral blood lymphocytes (hu-PBL-SCID mice) as an in vivo model for studying human IL-13. PBL from three donors (two allergic and one non-allergic) were prestimulated with IL-13 in vitro and thereafter transplanted into SCID mice. As evidenced by flow cytometry, IL-13 in the in vitro cell cultures was physiologically active and suppressed CD14 expression, while it enhanced the expression of CD23 on human monocytes. In the in vivo experiments, SCID mice transplanted with cells from both allergic donors produced twice as high maximum levels of IgE when the cells were preincubated with IL-13 in vitro before transplantation, as compared with mice receiving cells that had not been preincubated with IL-13. Two succeeding intraperitoneal (i.p.) injections of IL-13 resulted in a further increase of maximum IgE levels. Using cells from the non-allergic donor, no enhancing effect of IL-13 was observed. Transplanted human cells from one allergic donor examined were shown to migrate to the spleen and lungs of the recipient mice, while cells from the non-allergic donor were found only in the peritoneal cavity. Altogether, our results indicate that IL-13 enhances human IgE production in vivo and suggest that lymphocytes in allergic individuals are hyper-reactive to this cytokine. Furthermore, the allergic status of the cell donor may affect migration and engraftment of cells transplanted into SCID mice.

Animals↗
PubMed1999

Intranasal immunization with heat-inactivated Streptococcus pneumoniae protects mice against systemic pneumococcal infection.

In order to study the mucosal and serum antibody response to polysaccharide-encapsulated bacteria in mice, a preparation of heat-inactivated Streptococcus pneumoniae type 4 was administered, with and without cholera toxin, at various mucosal sites. It appeared that intranasal immunization of nonanesthesized animals was superior to either oral, gastric, or colonic-rectal antigen delivery with regard to the induction of serum immunoglobulin G (IgG) and IgA, as well as saliva IgA antibodies specific for pneumococci. The marked IgA antibody response in feces after intranasal, but not after oral or gastric, immunization is suggestive of a cellular link between the nasal induction site and the distant mucosal effector sites. Intranasal immunization also induced antibodies in serum and in mucosal secretions against type-specific capsular polysaccharide. IgA and IgG antibody levels in pulmonary lavage fluids correlated well with saliva IgA and serum IgG antibodies, respectively. Antibody determinations in pulmonary secretions may therefore be redundant in some cases, and the number of experimental animals may be reduced accordingly. After intraperitoneal challenge with type 4 pneumococci, mice immunized intranasally were protected against both systemic infection and death, even without the use of cholera toxin as a mucosal adjuvant. Thus, an efficient intranasal vaccine against invasive pneumococcal disease may be based on a very simple formulation with whole killed pneumococci.

Administration, Intranasal↗