SEARCH · PubMed Health

Results for “BALB/c mouse model”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 379 records · Page 21Linked to original sources

PubMed2000

The in vitro and in vivo pharmacology of antisense oligonucleotides targeted to murine Stat6.

OBJECTIVE AND DESIGN: This study was designed to establish whether phosphorothioate (PS) antisense oligonucleotides (AS-ODN) targeted to Stat6 were active in vivo in a mouse model of active sensitisation. MATERIALS: Female Balb/c mice (6-8) per group were used for in vivo study. TREATMENT: Mice were treated with active PS AS-ODNs determined in initial in vitro studies. Compounds were dosed daily (3-30mg/kg i.v.) over the course of sensitisation to ovalbumin. METHODS: Stat6 mRNA and protein levels were determined in the spleen after treatment (quantitative northern and western analysis respectively), in addition to serum IgE (ELISA). ANOVA was used to determine any significant differences between groups. RESULTS: Both of the AS-ODNs tested in vivo, down regulated Stat6 mRNA and protein levels in the spleen by 40-50% although there was no effect on serum IgE. These treatments also induced splenomegaly in vivo and caused splenocyte proliferation in vitro. CONCLUSIONS: The AS-ODNs used can down regulate Stat6 mRNA and protein although not sufficiently to influence IgE-levels. These effects are likely to be complicated in vivo by the immune-stimulation evident as splenomegaly.

Animals↗

PubMed2000

Flumazenil induces benzodiazepine partial agonist-like effects in BALB/c but not C57BL/6 mice.

RATIONALE: Some anxiety disorders may be treated in a different way than normal anxiety. OBJECTIVE: This study was aimed at investigating the action of the benzodiazepine receptor antagonist flumazenil, compared to that of the benzodiazepine receptor full agonist chlordiazepoxide, in an animal model of generalised anxiety disorder (the BALB/c mouse). METHODS: Flumazenil (0.0001, 0.001, 0. 01, 0.1 and 1 mg/kg) or chlordiazepoxide (5 mg/kg) were administered to BALB/c or C57BL/6 mice subjected to the light/dark test, the elevated plus maze or a passive avoidance step-through paradigm. RESULTS: Chlordiazepoxide and flumazenil (at all doses tested in the elevated plus maze and at the doses of 0.001 and 0.01 mg/kg in the light/dark test) induced a strong anxiolytic effect in BALB/c mice. Flumazenil did not induce anxiolysis in C57BL/6 mice, whatever the behavioral test or the dose used. However, chlordiazepoxide elicited anxiolysis in this strain in both procedures. In the passive avoidance test, chlordiazepoxide was amnesic in both strains but flumazenil had no effect. CONCLUSION: Flumazenil induces partial agonist-like effects in BALB/c and not in C57BL/6 mice, suggesting a possible benzodiazepine receptor set point shift toward the agonistic direction in some pathological anxiety states such as generalised anxiety disorder.

Animals↗

PubMed1994

Protection of infant mice from challenge with Streptococcus pneumoniae type 19F by immunization with a type 19F polysaccharide--pneumolysoid conjugate.

The immunogenicity and protective efficacy of a conjugate of Streptococcus pneumoniae type 19F polysaccharide and a genetically toxoided derivative of the pneumococcal toxin pneumolysin was investigated in an infant mouse model. The conjugate was administered to Balb/c mice during pregnancy and/or lactation, and to their offspring during early infancy. The anti-polysaccharide and anti-pneumolysin titres of the immunized infant mice were significantly higher than those of non-immunized controls. When the infant mice were challenged with type 19F pneumococci, the bacteria were cleared more effectively from the blood of immunized mice than from that of control mice. The survival rate for the immunized mice was also significantly higher than that for the control group. These results indicate that highly protective anti-pneumococcal responses can be induced in infant mice by immunization with the conjugate during gestation or early infancy, and suggest a possible role for pneumolysoid-polysaccharide conjugates as human vaccine components.

Animals↗

PubMed2005

Protection of inactivated influenza virus vaccine against lethal influenza virus infection in diabetic mice.

Influenza virus infection frequently causes complications and some excess mortality in the patients with diabetes. Vaccination is an effective measure to prevent influenza virus infection. In this paper, antibody response and protection against influenza virus infection induced by vaccination were studied in mouse model of diabetes. Healthy and diabetic BALB/c mice were immunized once or twice with inactivated influenza virus vaccine at various dosages. Four weeks after the first immunization or 1 week after the second immunization, the mice were challenged with influenza virus at a lethal dose. The result showed that the antibody responses in diabetic mice were inhibited. Immunization once with high dose or twice with low dose of vaccine provided full protection against lethal influenza virus challenge in diabetic mice, however, in healthy mice, immunization only once with low dose provided a full protection.

Animals↗

PubMed2004

Coordinated activation of VEGFR-1 and VEGFR-2 is a potent arteriogenic stimulus leading to enhancement of regional perfusion.

OBJECTIVE: The process of arteriogenesis is driven by various growth factors including vascular endothelial growth factor (VEGF)-A, which mediates its activity through VEGFR-2 (Flk-1/KDR) on endothelial cells and through VEGFR-1 (Flt-1) on endothelial cells and monocytes. The purpose of this study was to identify which of the VEGF receptors are involved in arteriogenesis in vivo. METHODS: Collateral vessel growth was induced by femoral artery ligation in a mouse model of hindlimb ischemia. Following ligation, Balb/c mice were treated with different growth factors (VEGF-A, VEGF-E, PlGF-2, VEGF-E plus PlGF-2 or VEGF-A plus PlGF-2, activating either VEGFR-1, VEGFR-2, or both). After 1 week of treatment, hindlimb perfusion was assessed by perfusion scintigraphy using Tc-99m-MIBI. RESULTS: The strongest improvement of regional perfusion was achieved by simultaneous activation of VEGFR-1 and VEGFR-2, using either VEGF-A or VEGF-A plus PlGF-2, with elevation of relative perfusion in the ischemic limbs from 0.61 to 0.83. The partial restoration in perfusion was associated with morphological changes typical for arteriogenesis. Moreover, specific inhibition of both VEGF-receptors using ZK 202650 resulted in a significant inhibition of arteriogenesis, indicating an active role of the VEGF system in compensatory arteriogenesis. CONCLUSION: The coordinated activation of both VEGFR-1 and VEGFR-2 represents a more potent arteriogenic stimulus compared to the isolated activation of either one of these two receptors. These data imply that the activation of both monocytes and endothelial cells is necessary to obtain a maximal VEGF-induced activation of arteriogenesis.

Animals↗

PubMed2005

Prophylactic and therapeutic intervention in IgE responses by biolistic DNA vaccination primarily targeting dendritic cells.

BACKGROUND: Allergen gene transfer represents an alternative approach to specific immunotherapy with allergen extracts. Gene gun-mediated DNA immunization with plasmid vectors expressing a transgene under control of the promoter of the fascin gene (pFascin) allows for antigen production predominantly by dendritic cells and resulted in the generation of CD8(+) cytotoxic T lymphocytes as well as in the development of a type 1 immune response. OBJECTIVE: We compared the in vivo efficiency of biolistic transfection with pFascin and plasmids containing the cytomegalovirus promoter (pCMV) in a mouse model of type I allergy. METHODS: BALB/c mice were sensitized with the model allergen beta-galactosidase to induce a distinctive type 2 immune response. The effect of prophylactic as well as therapeutic biolistic transfection with beta-galactosidase-encoding plasmids on the development of antibody titers was followed, and anaphylactic potential of sera was determined. Spleen cells were stimulated in vitro to analyze cytokine production and induction of CD8(+) effector T cells. RESULTS: Protective allergen gene transfer with pFascin efficiently prevented specific IgE production accompanied by immune deviation toward a T(H)1-polarized immune response as well as by the induction of IFN-gamma-producing CD8(+) effector T cells, being comparable to vaccination with pCMV. In a therapeutical setting, biolistic DNA vaccination with pFascin or pCMV transiently protected allergen-sensitized mice against the strong increase in specific IgE production caused by subsequent allergen challenge. CONCLUSION: We demonstrate for the first time that restricting transgene expression primarily to dendritic cells after DNA vaccination suffices to cause inhibition of IgE production prophylactically and therapeutically.

Animals↗

PubMed2006

High expression of survivin and down-regulation of Stat-3 characterize the feto-maternal interface in failing murine pregnancies during the implantation period.

The materno-fetal interface has for long been considered as an immune privileged biological site and thus understanding the mechanisms underlying fetal survival have been the focus of intense research. In adults, survivin and Stat-3 proteins are involved in tolerance as well as the induction of apoptosis. However, the role of these molecules in pregnancy and development has not been addressed. We have evaluated the expression of survivin and Stat-3 in allogeneic mouse models of low abortions (CBA/J x Balb/c), abortion prone (CBA/J x DBA/2J) and stress-triggered abortions from DBA/2J-mated CBA/J mice. We show that survivin is over-expressed in abortion-prone mating on gestation day 7.5. This effect was also found in stress-exposed mice, whereas expression was low in normal pregnancy mice. The phosphorylated Stat-3 (p-Stat-3) was down regulated in high abortion mating compared with low abortion mating, CBA/J x Balb/c. The level of apoptosis was similar in the three groups studied. Our results suggest that high expression of survivin and low expression of p-Stat-3 are involved in pregnancy loss in mice.

Abortion, Spontaneous↗

PubMed1998

Protective effects of equine herpesvirus-1 (EHV-1) glycoprotein B in a murine model of EHV-1-induced abortion.

In an attempt to determine if pregnant mice could be protected from abortion subsequent to challenge with equine herpesvirus-1 (EHV-1) in the mouse model of EHV-1 disease, female BALB/c mice were inoculated with baculovirus-expressed EHV-1 glycoprotein B (bac-gB), wild-type baculovirus (bac-wt), rabbit kidney (RK-13) or baby hamster kidney (BHK-21) cells. Using an ELISA, antibodies against EHV-1 were detected in the serum of mice following two injections of bac-gB and were enhanced by a third injection, after which low levels of neutralising antibody were also detected. After mating, mice in the bac-gB, bac-wt and RK-immunised groups were infected intranasally with 10(7) pfu of EHV-1 on day 16 of pregnancy. All challenged mice experienced body weight loss post-infection (pi). However, postnatally, the gB-immunised group demonstrated body weight gain which was not seen in the other groups. There were no maternal deaths in the gB-immunised group but 1/6 bac-wt-immunised and 3/6 RK-immunised mice died post-challenge. Litter survival rate was significantly higher (p < 0.001) for the gB-immunised dams (54%) than that of either the bac-wt-(9%) or RK-immunised (0%) dams and the mean body weight of young from the surviving bac-wt-immunised litter was significantly (p = 0.021) lower than either the gB-immunised group or the BHK-immunised unchallenged group at 10 days of age. The virus was not isolated from any foetus from a gB-immunised dam. However, the virus was detected in 9% of foetuses from bac-wt-immunised and 21% of foetuses from RK-immunised dams.

Abortion, Veterinary↗

PubMed2001

Antisense therapy of influenza.

The liposomally encapsulated and the free antisense phosphorothioate oligonucleotides (S-ODNs) with four target sites (PB1, PB2, PA, and NP) were tested for their abilities to inhibit virus-induced cytopathogenic effects by a MTT assay using MDCK cells. The liposomally encapsulated S-ODN complementary to the sites of the PB2-AUG initiation codon showed highly inhibitory effects. On the other hand, the inhibitory effect of the liposomally encapsulated S-ODN targeted to PB1 was considerably decreased in comparison with those directed to the PB2 target sites. The liposomally encapsulated antisense phosphorothioate oligonucleotides exhibited higher inhibitory activities than the free oligonucleotides, and showed sequence-specific inhibition, whereas the free antisense phosphorothioate oligonucleotides were observed to inhibit viral absorption to MDCK cells. Therefore, the antiviral effects of S-ODN-PB2-AUG and PA-AUG were examined in a mouse model of influenza virus A infection. Balb/c mice exposed to the influenza virus A (A/PR/8/34) strain at dose of 100 LD(50)s were treated i.v. with various doses (5-40 mg/kg) of liposomally (Tfx-10) encapsulated PB2-AUG or PA-AUG before virus infection and 1 and 3 days postinfection. PB2-AUG oligomer treated i.v. significantly prolonged the mean survival time in days (MDS) and increased the survival rates with a dose-dependent manner. We demonstrate the first successful in vivo antiviral activity of antisense administered i.v. in experimental respiratory tract infections induced with influenza virus A.

Animals↗

PubMed1979

Murine cutaneous leishmaniasis: disease patterns in intact and nude mice of various genotypes and examination of some differences between normal and infected macrophages.

The course of the disease, cutaneous leishmaniasis, caused by the intracellular protozoan parasite Leishmania tropica, differs markedly amongst various common inbred mouse strains. After intradermal injection of 1 x 10(6) promastigotes to young female specific pathogen-free (SPF) derived mice, persistent infection characterized by an expanding ulcerous lesion is seen in BALB/c and DBA/2 mice. In the strains CBA/H, C3H/He and A/J, lesions resolve within 8 weeks, and in C57B1/6 mice no real lesion typical of cutaneous leishmaniasis develops at the injection site. NZB mice are highly resistant. Macrophages harvested from the thioglycollate-stimulated peritoneal cavity of NZB and C57B1/6 mice appear to differ from macrophages of the other mouse strains in not supporting multiplication of L. tropica organisms in vitro. Nevertheless, hypothymic nude (nu/nu) mice of C57B1/6 genotype, as well as CBA/H-nu/nu and BALB/c-nu/nu mice, develop large lesions with metastases to other cutaneous and visceral locations. In the intact mice in which infection resolves spontaneously, resistance to reinfection is complete. Using mouse antipromastigote sera and an indirect fluorescent antibody test in carefully controlled experiments, L. tropica antigens were detected on in vitro infected macrophages of both highly susceptible BALB/c and relatively resistant CBA/H genotypes. After incubation with a crude soluble antigen preparation from cultured promastigotes, infected BALB/c macrophages differed from infected CBA/H macrophages (and uninfected macrophages of both genotypes) in being unable to sensitize syngeneic recipients for a delayed-type hypersensitivity response to that antigen. When infected and uninfected macrophages were used as "blocking cells" in an in vitro alloreactive cytotoxic T cell system involving cells from congenic mice, evidence was obtained for reduced H-2d expression on infected macrophages of the susceptible mouse strains, BALB/c. The data in this model system of cutaneous leishmaniasis raise the possibility that genetic susceptibility is associated with both a permissive macrophage and defective T cell recognition of parasite antigens on infected macrophages. Defective recognition may be the result of reduced functional expression of H-2d antigens on infected BALB/c macrophages required for efficient recognition by syngeneic T cells of one or more subpopulations.

Animals↗

PubMed1985

The thiol groups of mouse immunoglobulin A. Incomplete formation of the C alpha 1-domain disulphide bridge.

The BALB/c IgA (immunoglobulin A) myeloma protein M167 contained on average 5.7 free SH groups per IgA dimer. These groups were preponderantly on the heavy chains and comprised two distinct populations: 3.3 exposed SH groups per dimer in the Fc region, and 2.4 buried SH groups per dimer in the Fd region, detectable o only after denaturation. To locate the cysteine residues involved, labelled peptides were purified from thermolysin digests of radioalkylated IgA by high-performance liquid chromatography. From the amino acid compositions of the peptides, the exposed thiol groups were assigned to Cys-307 in the C alpha 2 domain, which thus existed in the reduced form to an extent exceeding 80%. This residue may allow attachment of secretory component to dimer IgA in the mouse to proceed via thiol-disulphide exchange. The buried thiol groups were assigned to Cys-150 and Cys-208, in the C alpha 1 domain, each being in the reduced form to the extent of approx. 30%. This pair of residues would normally give rise to the characteristic intradomain disulphide bridge. It appears that disulphide formation is not a crucial event during folding of the C alpha 1 domain in IgA biosynthesis. The sequence in the region 140-151 was re-investigated, and residue 142 was shown to be serine, not cysteine, helping explain the lack of heavy-chain-light chain bonding in BALB/c mouse IgA. A disulphide-bond model for mouse IgA is proposed on the basis of these assignments and other features of the mouse alpha-chain sequence.

Animals↗

PubMed2001

Gammadelta T cells assist alphabeta T cells in the adoptive transfer of contact hypersensitivity to para-phenylenediamine.

Para-phenylenediamine (PPD) is known to be a common sensitizer of allergic contact dermatitis and contact urticaria. To clarify the mechanism of contact hypersensitivity (CHS) to PPD, we established a mouse model of PPD-induced CHS. BALB/c mice were immunized for 3 consecutive days by painting topically a 2.5% PPD solution on their shaved abdominal skin. On days 5, 7 or 9 after the initial application, the mice were challenged by applications of a 2.5% PPD solution. Maximal ear swelling was determined at 24 h but another statistically significant and smaller ear swelling was observed 1 h after challenge with PPD in a hapten-specific manner. Adoptive cell transfer experiments demonstrated that the ear swelling of the adoptive cell transferred mice displayed an early response at 6 h and a late response from 12 h to 24 h when the recipient mice were challenged immediately after transfer. Both MoAbs and complement treatment of the transferred cells demonstrated that the phenotype of the early response cells which elicited a response at 6 h after challenge was Thy1(+), B220(+), alphabeta TCR(-), gammadelta TCR(-), CD3(-), CD4(-), CD5(+) and CD8(-). The in vitro treatment of effector cells with MoAbs against not only alphabeta TCR but also gammadelta TCR, together with complement, was found to diminish substantially the late response, elicited 12-24 h after challenge. Gammadelta T cells reconstituted the ability of alphabeta T cells to transfer 24 h CHS responsiveness. The phenotype of the gammadelta T cells that assist CHS effector alphabeta T cells was CD3(+), CD4(-) and CD8(+) and these regulatory gammadelta T cells were neither Ag-specific nor MHC-restricted. Furthermore, gammadelta T cells from normal spleen could also assist alphabeta T cells in adoptive transfer of the 24 h CHS response in a non-MHC-restricted manner. RT-PCR demonstrated that alphabeta T cells strongly expressed mRNA IFN-gamma, whereas gammadelta T cells expressed not only IFN-gamma but also IL-4 and IL-10. These data indicate that not only early response cells and alphabeta T cells but also Th2 type gammadelta T cells may play an important role in the elicitation of CHS to PPD.

Adoptive Transfer↗

PubMed2000

Mutual boosting effects of sensitization with timothy grass pollen and latex glove extract on IgE antibody responses in a mouse model.

Type I allergy to natural rubber latex can be an important health problem for latex-exposed individuals (e.g., health care workers, spina bifida children). Also beyond these risk groups, a high sensitization rate of varying and partly unknown clinical relevance has been reported. Atopy represents a risk factor for latex allergy and recent studies indicate that patients suffering from pollen allergies may have pollen allergen-specific IgE antibodies which cross-react with latex allergens. In order to investigate whether sensitization to pollen allergens can have priming effects on the production of IgE antibodies against latex in vivo, a mouse model was established. Groups of 10 BALB/C mice were immunized with Al(OH)3-adsorbed pollen extracts from timothy grass, ragweed, mugwort, or birch. For control purposes, one additional group received adjuvant only and another group was not immunized. Half of the mice of each group were subsequently immunized with Al(OH)3-adsorbed latex glove extract, the other half with adjuvant only. Pollen and latex-specific IgE- and IgG1-antibody responses were analyzed by enzyme-linked immunosorbent assay and statistically evaluated by analysis of variance. Antibody responses to cross-reactive antigens were investigated by immunoblotting. We found significantly increased IgE reactivities to latex after pollen sensitization and vice versa. Moreover, mice immunized with timothy grass pollen extract alone - without subsequent latex immunization - displayed IgE reactivity to latex. Cross-reactive antibodies were directed against pollen antigens of approximately 60 kDa molecular weight. Our results thus demonstrate a mutual boosting effect of pollen and latex sensitization in vivo which may be also operative in polysensitized plant allergic patients.

Allergens↗

PubMed1992

Testosterone regulates epidermal growth factor levels in the thyroid gland of hypothyroid mice.

The effects of testosterone (TP) and thyroxine (T4) on the level of epidermal growth factor (mEGF) in the thyroid were compared in a hypothyroid mouse model. Groups of five adult female BALB/c mice were given a "severe" hypothyroid regimen consisting of an iodine deficient diet together with oral and s.c propylthiouracil (PTU). Sialoadenectomy or sham operation was performed after 18 days on the hypothyroid regimen. The mice convalesced on normal diet for 5 days and beginning from day 23 received either T4, 1 ug/g or 2 ug/g, s.c daily or TP, 0.3 mg or 0.75 mg, i.m. every third day until day 33, while continuing the hypothyroid regimen. Control mice received normal diet and vehicles for the various injections. The mice were killed on day 33 and thyroidal EGF levels determined by radioimmunoassay. The mean+S.E. levels of mEGF in the thyroid were 10.12 +/- 1.75 ng/mg protein (control), 3.82 +/- 0.67 ng/mg (hypothyroid; p < 0.01), 3.07 +/- 1.52 (T4, 1 ug/g; p < 0.02), 2.59 +/- 0.46 ng/mg (T4, 2 ug/g; p < 0.01), 8.58 +/- 2.48 (TP, 0.3 mg), and 9.65 +/- 1.86 (TP, 0.75 mg). Thus thyroidal mEGF levels decreased significantly in all groups except those subsequently treated with testosterone; T4 was ineffective in reversing the tissue depletion of mEGF in this model. These results show that mEGF levels in the thyroid could be depleted by hypothyroidism and may also be androgen responsive.

Animals↗

PubMed1974

IgM-producing tumors in the BALB-c mouse: a model for B-cell maturation.

Five adjuvant induced BALB/c tumors producing IgM-McPc 1748, W 3469, TEPC 183, McPc 774, and Y 5781-were characterized morphologically by electron microscopy, analysis of the distribution of surface-bound and intracytoplasmic IgM using immunofluorescence, and by biochemical study of IgM synthesis, turnover, and secretion. The cells of different tumors appear to represent different stages in B-cell maturation when compared to normal, lipopolysaccharide-stimulated B cells. Thus, McPc 1748 tumor cells resemble 10-25-h stimulated normal B cells, 3469 cells resemble 20-35-h stimulated B cells, TEPC 183 cells resemble 45-65-h stimulated B cells, Y 5781 cells resemble 80-110-h stimulated B cells, and McPc 774 cells resemble 100-130-h stimulated B cells.

Animals↗

PubMed2005

Rejection patterns in allogeneic uterus transplantation in the mouse.

BACKGROUND: Transplantation of the uterus in the mouse has been developed as a model system for research towards human uterine transplantation. Previous studies in a mouse model have demonstrated that a syngeneic uterus transplant can give rise to normal offspring. The aim of this study was to characterize the time course of rejection in a fully allogeneic mouse uterus transplantation model. METHODS: Uteri of BALB/c mice were transplanted to a heterotopic position in C57BL/6 recipients, whose native uteri were left in situ. The blood flow of the uteri, their gross appearance and general histology and the density of T-lymphocytes were examined on postoperative days 2-28. RESULTS: Macroscopic signs of rejection were apparent from day 5. At the light microscopy level, minimal inflammatory changes were seen from day 5 and massive inflammation was seen from day 10 to day 15. At day 28, necrosis and fibrosis were seen. The density of T-lymphocytes (CD3(+)) was increased in the grafted uterus from day 2 in the myometrium and from day 5 in the endometrium. Blood flow in the grafted uteri was reduced from day 15. CONCLUSION: A murine model to study rejection of allogeneic uterus transplants was characterized. Signs of rejection were seen from day 2 to day 5 and severe rejection was seen from day 10 to day 15. The data will be useful in future studies on immunosuppressants in this model.

Animals↗

PubMed1997

Transmission of equine herpesvirus 2 to the mouse: characterization of a new laboratory infection model.

Intranasal inoculation of BALB/c mice with a recent clinical isolate of equine herpesvirus 2 (EHV-2 strain MR) produced a productive infection characterized by clinical signs, including weight-loss and conjunctivitis, but no mortality. Infectious virus was isolated from the lung, trachea and nasal turbinates with the highest titres present in lung tissue; EHV-2 neutralizing antibody was detected in the serum on day 21 post-inoculation. No infectious virus was detected in neural tissue, blood or lymphoid tissues. An EHV-2-specific nested PCR confirmed the presence of EHV-2 DNA in the respiratory tissues. In addition, EHV-2 DNA was detected in the trigeminal ganglia and olfactory bulbs from the first day after inoculation and these tissues remained positive for EHV-2 DNA for at least 30 days, by which time EHV-2 DNA had been cleared from all other tissues.

Animals↗

PubMed2005

Prenatal lipopolysaccharide-exposure prevents allergic sensitization and airway inflammation, but not airway responsiveness in a murine model of experimental asthma.

BACKGROUND: Epidemiological evidence underlines the impact of prenatal environmental factors on the development of postnatal allergies. In this regard an inverse correlation between lipopolysaccharide (LPS) exposure and development of childhood allergy has been found. OBJECTIVE: To assess the impact of prenatal LPS exposure on the development of postnatal respiratory allergies in a mouse model of experimental asthma. METHODS: Female BALB/c mice were exposed to LPS before conception and during pregnancy. Several weeks after birth offspring were sensitized to ovalbumin (OVA) followed by aerosol allergen challenges. RESULTS: Prenatal, maternal LPS-exposure enhanced neonatal IFN-gamma, but not IL-4 and IL-2 production. OVA sensitization of prenatally LPS-exposed mice was accompanied by a marked suppression in anti-OVA IgG1 and IgE as well as unchanged IgG2a antibody responses, paralleled by a significant reduction in IL-5 and IL-13 levels following mitogenic stimulation of splenic leucocytes. Assessment of bronchoalveolar lavage fluids following allergen challenges revealed a marked reduction in eosinophils and macrophages in these mice. Surprisingly, development of airway hyper-responsiveness, a hallmark of bronchial asthma, was not affected. CONCLUSION: This study provides first experimental evidence that LPS may already operate in prenatal life in order to modulate the development of allergies in the offspring.

Animals↗