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Biomedical subjects

M Løvik

Publications and source records attributed to M Løvik.

At least 37 records · Page 2Linked to original sources

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.

Animals↗

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.

Allergens↗

Protective effect of beta-glucan against mycobacterium bovis, BCG infection in BALB/c mice.

Beta-1,3-glucan is a potent stimulator of macrophage functions and has a protective effect against a range of infections in rodent models. We examined whether the agent could also protect against the intracellular Mycobacterium bovis, bacillus Calmette-Guérin (BCG) infection in mice. BCG-susceptible BALB/c mice were injected intravenously (i.v.) with beta-glucan or vehicle 3 days before, or with beta-glucan 7 days after i.v. challenge with live BCG bacilli. The animals were killed 4 or 8 weeks later, their organs were homogenized and applied to object slides and stained with auramin for counting of bacilli, or seeded onto agar in Petri dishes. Mice treated with beta-glucan both pre- and postchallenge had significantly lower numbers of BCG bacilli and BCG colony-forming units in spleen homogenates compared with controls 4 weeks after challenge. A similar, but not statistically significant, tendency was observed in spleen homogenates from mice killed 8 weeks after challenge. In homogenates of liver and lungs there were similar findings, but less pronounced. There was a dose-dependent effect of beta-glucan injected before BCG challenge on the number of BCG bacilli found in spleen and liver homogenates. In addition, antibody cross-reactivity was demonstrated between M. tuberculosis cell wall and beta-glucan. The results suggest that beta-glucan has a protective effect against M. bovis, BCG infection in susceptible mice.

Animals↗

Diesel exhaust particles and carbon black have adjuvant activity on the local lymph node response and systemic IgE production to ovalbumin.

The possible adjuvant effect of diesel exhaust particles (DEP) on the response to the model allergen ovalbumin (OA) was studied in BALB/c mice using the popliteal lymph node (PLN) assay. In addition to changes in PLN weight, cell numbers and cell proliferation, specific serum IgE anti-OA antibody levels were measured. OA inoculated together with DEP into one hind footpad gave a significantly augmented response (increase in weight, cell numbers and cell proliferation) in the draining popliteal lymph node as compared to DEP or OA alone. Also, the local lymph node response was of longer duration when DEP were given with the allergen. Experiments in thymus-deficient nu/nu mice indicated that the lymph node response observed in BALB/c mice was of a specific immunologic character and not an unspecific inflammatory reaction. The OA-specific IgE response was increased in mice receiving OA together with DEP as compared to the response in mice receiving OA without DEP. Carbon black (CB) was given with and without OA in some experiments, as a surrogate for the non-extractable core of DEP. CB was found to resemble DEP in its capacity to increase the local lymph node response and serum specific IgE response to OA, but CB appeared to be slightly less potent than DEP. Thus, both DEP and CB had a significant adjuvant effect on the local immune-mediated inflammatory response and on the systemic specific IgE response to allergen. The results indicate that the non-extractable particle core contributes substantially to the adjuvant activity of DEP.

Adjuvants, Immunologic↗

Mutant and transgenic mice in immunotoxicology: an introduction.

An overview is given in simple terms of the techniques behind transgenic, knock-out and knock-in mice. The principles for the creation and use in toxicology of genetically engineered animals are outlined, and some examples are given from areas related to immunotoxicology. Genetically engineered animals have so far been used only to a very limited extent in immunotoxicology. Practical aspects of work with transgenic animals are discussed, and sources of information and services related to transgenic animals are listed.

Allergy and Immunology↗

[Do infections reduce the development of allergy? Do measles reduce the risk of allergic disease?].

Immunological theory indicates that infections can prevent allergy by directing the immune reaction against an antigen towards a Th1-type response, thus inhibiting an allergy-associated Th2-type response. The author briefly reviews the evidence indirectly supporting the theory that infections early in life reduce risk of atopy: the protective effect of having older siblings, the increasing risk of atopy with a higher standard of living, and higher prevalence of atopy in Western Europe than in the former communist countries in the East. A new study from Guinea-Bissau is cited, demonstrating an apparently strong protective effect of measles infection in relation to the risk of being skin test positive to common allergens. The medical and ethical questions raised by these findings are pointed out: do we have to choose between measles and an increase in allergic diseases? And if so, who should decide-the individual or society?

Humans↗

Total and birch pollen-specific human IgE in mice with severe combined immunodeficiency transplanted with human peripheral blood lymphocytes: donor dependence, seasonal variation and in vivo half-life.

BACKGROUND: There is a need for animal in vivo models in the study of human allergy. The aim of the present experiments was to study production and catabolism of human IgE in mice with severe combined immunodeficiency transplanted with human peripheral blood lymphocytes (hu-PBL-SCID mice). METHODS: Groups of SCID mice were transplanted intraperitoneally with hu-PBL from the same three donors in five experiments. Subgroups of transplanted mice were immunized with birch pollen. Production of human total and birch pollen-specific IgE in the hu-PBL-SCID mice was analyzed over a 7-week period. RESULTS: Human IgE was detected in 93% of the hu-PBL-SCID mice, and the production showed reproducible donor-dependent kinetics. Production of birch pollen-specific human IgE, however, was seen only in mice transplanted with cells from birch pollen-allergic donors. A greater proportion of the mice produced specific IgE when the experiment was started in, or some months after a birch pollen season with high pollen counts. The half-lives of passively transferred human IgE were determined to be 24.0 and 23.4 h for total and birch pollen-specific IgE, respectively. CONCLUSIONS: This study demonstrates that human IgE production in hu-PBL-SCID mice is very reproducible when the same donor is used several times. Specific IgE production in recipient mice seems to require the use of cell donors with the actual specific allergy, and is most readily obtained during or after a period of donor allergen exposure. The short half-lives found indicate that hu-PBL-SCID mice have a high ongoing production of human IgE.

Allergens↗

The impact of exposure group on the progression rate to acquired immunodeficiency syndrome. A comparison between intravenous drug users, homosexual men and heterosexually infected subjects.

The objective was to study the impact of exposure group on the progression rate to the acquired immunodeficiency syndrome (AIDS). 289 subjects in Oslo, Norway, infected with the human immunodeficiency syndrome (HIV) and without major clinical signs of HIV infection (102 intravenous drug users, 151 homosexual men and 36 heterosexually infected subjects) were recruited to the Oslo HIV Cohort Study from 1989 and followed until 1 January 1995. 15 (14.7%) of the intravenous drug users, 56 (37.1%) of the homosexual men and 5 (12.5%) of the heterosexually infected subjects developed AIDS during a mean time of 47 months (p < 0.001, log rank test). When controlling for possible confounding variables (age, number of CD4+ lymphocytes, antiviral therapy at study entry, gender and year of HIV diagnosis), the relative risk of AIDS progression was 2.2 [1.1-4.5, 95% confidence interval (CI)] for homosexual men and 0.5 (0.2-1.3, 95% CI) for heterosexually infected subjects as compared to intravenous drug users. In a subgroup with known time of seroconversion (n = 60), 47% (18/38) of the homosexual men, 20% (3/15) of the intravenous users and none (0/7) of the heterosexually infected subjects developed AIDS (p = 0.04, log rank test). The results suggest that homosexual men have more rapid progression to AIDS than intravenous drug users and heterosexually infected subjects.

Acquired Immunodeficiency Syndrome↗

Enhancement of Streptococcus pneumoniae serotype 6B infection in mice after passive immunization with human serum.

Passive immunization in an experimental pneumococcal infection model has been proposed as a way to further characterize the protective capacity of human post vaccination sera. However, in experiments described in the present paper, we found that the same human immune serum that induced some degree of protection when NIHS mice were challenged with one strain of Streptococcus pneumoniae serotype 6B, did not confer protection when the mice were challenged with another strain of serotype 6B. On the contrary, with this bacterial strain, six different human sera appeared to enhance pneumococcal infection leading to higher levels of bacteremia and more rapid death of passively immunized than of non-immunized mice. In contrast, mice passively immunized with mouse immune serum showed reduced bacteremia and enhanced survival after challenge with the same dose of the same strain of pneumococci. The enhancing property of human serum did not seem to be caused by anti-type 6B antibodies. However, we cannot exclude the possibility that human antibodies are less protective than mouse antibodies against type 6B infection. Our results indicate that negative results in passive immunization experiments with human sera should be interpreted with caution.

Animals↗

Human antibody response to a pneumococcal vaccine in SCID-PBL-hu mice and simultaneously vaccinated human cell donors.

Severe combined immunodeficient (SCID) mice were transplanted intraperitoneally with human peripheral blood lymphocytes (PBL) from nine healthy human donors (SCID-PBL-hu mice). None of the donors had ever received pneumococcal vaccine. Ten days after transplantation, 62 out of 111 transplanted mice and six of the nine donors were vaccinated with a 23-valent pneumococcal polysaccharide vaccine. For each donor, human IgG was detected in 91.7-100% of the SCID-PBL-hu mice, whereas specific human IgG antipneumococcal antibodies were demonstrated in 16.7-100% of the vaccinated SCID-PBL-hu mice. Most of the mice transplanted with cells from the same donor showed similar antibody response patterns in terms of kinetics and antibody levels. A significant antibody response was only obtained in mice that received cells from donors with relatively high antipneumococcal antibody levels at the time of transplantation, or donors that showed a substantial increase in antibody levels after vaccination. The immune response in the SCID-PBL-hu mice did not always reflect the ability of the respective donor to produce antipneumococcal antibodies. The donor dependency of the antipneumococcal antibody response has great practical importance for the use of the SCID-PBL-hu model. Donors should not be chosen randomly. By selecting donors whose cells have been found to result in successful engraftment, functional SCID-PBL-hu mice can be obtained for the study of human immune responses and function in an in vivo experimental model.

Adult↗

The antibody response after immunization with pneumococcal polysaccharide vaccine in splenectomized mice: the effect of re-immunization with pneumococcal antigens.

Splenectomized individuals are at increased risk of acquiring fulminant pneumococcal infections. In an experimental mouse model, we have studied how removal of the spleen influences the anti-pneumococcal antibody response to s.c. primary immunization with a 23-valent pneumococcal polysaccharide vaccine and to re-immunization 5 months later. In splenectomized BALB/c mice the antibody response to serotypes 1, 4, 7F, and 19F was reduced both after the first and after the second immunization, compared to that in normal mice. In contrast, splenectomized and normal CBA/J mice produced similar antibody levels to serotypes 1 and 4 after the second immunization, although the response to these serotypes was reduced in splenectomized mice after the first immunization. After i.v. injection with heat-killed pneumococci serotype 4, splenectomized BALB/c mice that had been immunized 5 months earlier with 23-valent vaccine were able to mount higher antibody levels which were reached earlier than in unprimed splenectomized mice. However, normal mice that had been vaccinated 5 months earlier had the highest antibody levels after immunization with pneumococci. Our results indicate that although splenectomized mice generally do not reach as high antibody levels as are seen in normal mice after pneumococcal immunization, they benefit from previous immunization with regard to antibody levels when given a second antigen challenge.

Animals↗