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Results for “BALB/c mouse model”

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PubMed2003

LF 15-0195, a novel immunosuppressive agent prevents rejection and induces operational tolerance in a mouse cardiac allograft model.

BACKGROUND: LF 15-0195 (LF) is a new analogue of 15-deoxyspergualin (DSG) that is less toxic and more potent than DSG. The present study was undertaken to determine (1). the dose response of LF monotherapy, (2). its ability to induce tolerance, and (3) its interaction with cyclosporine (CsA), FK 506 (FK), and rapamycin (RAPA). METHODS: Varying doses of LF were administered to determine dose-dependent effects on graft survival in a C57BL/6 to BALB/c heterotopic heart allograft mouse model. Transplanting-donor and third-party skin grafts into long-term survivors were used to assess the tolerance status. CsA, FK, and RAPA were combined with LF to determine their interactive effects on graft survival. RESULTS: The efficacy and toxicity of LF was dose dependent. High-dose LF monotherapy (>2 mg/kg) induced donor-specific operational tolerance, but it was associated with high mortality. Simultaneous administration of high-dose calcineurin inhibitors (CsA FK) prevented tolerance induced by LF. In contrast, a short course of LF combined with a subtherapeutic dose of CsA FK achieved indefinite survival of C57/BL6 cardiac allografts. RAPA and LF had a synergistic effect in induction of tolerance. CONCLUSIONS: The efficacy and toxicity of LF were dose dependent. A short course of LF significantly reduced the requirement of CsA or FK to prevent rejection. RAPA and LF had synergy in induction of tolerance. These data indicate that LF may be a promising agent that warrants further studies in nonhuman primate models of transplantation.

Animals↗

PubMed2006

Mycobacterium bovis BCG substrains confer different levels of protection against Mycobacterium tuberculosis infection in a BALB/c model of progressive pulmonary tuberculosis.

Mycobacterium bovis BCG is the only available vaccine against tuberculosis. Reasons for why diverse BCG substrains induce different levels of protection in clinical trials remain unclear. The aim of this study was to compare the effectiveness of 10 BCG substrains in a mouse model of pulmonary tuberculosis. BALB/c mice were subcutaneously vaccinated and 2 months later were challenged with Mycobacterium tuberculosis H37Rv by intratracheal injection. Two and 4 months after challenge, delayed-type hypersensitivity (DTH) response, lung tissue affected by pneumonia, CFU, T-cell counts, and cytokine expression (interleukin-2 [IL-2], IL-4, IL-10, and gamma interferon) were determined. A differential protective effect of the diverse BCG substrains was found. BCG Phipps led to the largest and most persistent reduction of CFU counts and of the area of pneumonia at 2 and 4 months after challenge. This protection was accompanied by reduced IL-10-producing T cells. Contemporary BCG substrains induce a wide range of protection in this animal model. These data can help in the selection of the best vaccine for human immunization and for the development of novel recombinant BCG-based vaccine.

Animals↗

PubMed2001

Activities of hexadecylphosphocholine (miltefosine), AmBisome, and sodium stibogluconate (Pentostam) against Leishmania donovani in immunodeficient scid mice.

In both scid and BALB/c mouse-Leishmania donovani models, hexadecyphosphocholine (miltefosine) and AmBisome had similar levels of activity. In contrast, sodium stibogluconate (Pentostam) was significantly less active against L. donovani in scid mice than in BALB/c mice. The in vitro anti-leishmanial activity of miltefosine was similar in peritoneal macrophages derived from both scid and BALB/c mice, whereas Pentostam and AmBisome were significantly more active in the latter.

Amphotericin B↗

PubMed2004

alpha-Lipoic acid inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma.

BACKGROUND: Oxidative stress may play an important role in the pathogenesis of bronchial asthma. OBJECTIVE: We evaluated the therapeutic effect of alpha-lipoic acid, a nonenzymatic antioxidant, in a mouse model of asthma. METHODS: BALB/c mice were immunized intraperitoneally with ovalbumin (OVA) on days 1 and 14 and challenged with inhaled OVA on days 28, 29, and 30. Mice were fed OVA-free standard mouse chow with 0%, 0.125%, 0.25%, 0.5%, and 1% (wt/wt) alpha-lipoic acid during the immunization and challenge periods. On day 31, mice were challenged with inhaled methacholine, and enhanced pause was measured as an index of airway hyperresponsiveness. Severity of airway inflammation was determined by means of differential cell count of bronchoalveolar lavage (BAL) fluid and by means of histopathologic lung analysis. Levels of OVA-specific IgE in serum, IL-4 and IL-5 in BAL fluid, and intracellular reactive oxygen species in alveolar macrophages and lymphocytes obtained from regional perihilar lymph nodes were measured. Nuclear factor kappaB DNA-binding activity in lung tissues was analyzed by means of electrophoretic gel mobility shift assay. RESULTS: Compared with untreated asthmatic mice, mice treated with alpha-lipoic acid had significantly reduced airway hyperresponsiveness, a lower proportion of eosinophils among BAL cells, and significantly improved pathologic lesion scores of the lungs. alpha-Lipoic acid also significantly reduced serum OVA-specific IgE concentrations, IL-4 and IL-5 concentrations in BAL fluid, and intracellular reactive oxygen species and nuclear factor kappaB DNA-binding activity. CONCLUSION: These results suggest that oxidative stress plays an important role in asthmatic airway inflammation and that alpha-lipoic acid may be useful as adjuvant therapy for bronchial asthma.

Animals↗

PubMed2006

An essential role for dendritic cells in human and experimental allergic rhinitis.

BACKGROUND: In allergic rhinitis (AR) CD4(+) T(H)2 lymphocytes control inflammation by secreting T(H)2 cytokines, but little is known about how these cells are activated to cause disease. OBJECTIVE: We sought to study the contribution of antigen-presenting dendritic cells (DCs) in activating T(H)2 cells and controlling allergic inflammation. METHODS: Nasal mucosal biopsy specimens were taken from patients with house dust mite allergy and perennial AR and healthy control subjects. DC numbers were evaluated by using immunohistochemistry. The functional role of DCs was studied in a novel mouse model for AR using BALB/c mice and CD11c-diphtheria toxin (DT) receptor transgenic mice. RESULTS: In symptomatic patients with perennial AR, the number of CD1a(+) and CD11c(+) MHCII(+) DCs was higher in the epithelium and lamina propria of the nasal mucosa compared with that seen in healthy control subjects. In patients with AR, DCs had a more mature (CD86(+)) phenotype and were found in close approximation with T lymphocytes. Similarly, in a mouse model of ovalbumin (OVA)-induced AR, CD11c(+) DCs accumulated in areas of nasal eosinophilic inflammation and clustered with CD4(+) T lymphocytes. CD11c(+) DCs were conditionally depleted during allergen challenge by means of systemic administration of DT to CD11c-diphtheria toxin receptor transgenic mice to address the functional role of DCs in maintaining inflammation. In the absence of CD11c(+) DCs, nasal OVA challenge in OVA-sensitized mice did not induce nasal eosinophilia and did not boost OVA-specific IgE levels or T(H)2 cytokine production in the cervical lymph nodes. Conversely, when OVA-pulsed DCs were administered intranasally to sensitized mice, they strongly enhanced OVA-induced nasal eosinophilia and T(H)2 cytokine production. CONCLUSIONS: These data in human subjects and mice suggest an essential role for nasal DCs in activation of effector T(H)2 function leading to AR. CLINICAL IMPLICATIONS: Nasal DCs play an essential role in AR and therefore constitute a novel target for therapeutic intervention.

Animals↗

PubMed2001

Induction of strong hepatitis B virus (HBV) specific T helper cell and cytotoxic T lymphocyte responses by therapeutic vaccination in the trimera mouse model of chronic HBV infection.

Humanized BALB/c mice (termed trimera mice) conditioned by lethal total body irradiation and bone marrow transplantation from SCID mice have been described to support rapid engraftment of human peripheral blood mononuclear cells (PBMC) and the induction of strong B and T cell responses after immunization in vivo. Moreover, these mice can be infected with the hepatitis B and C viruses (HBV, HCV). The current study employed this model to study therapeutic vaccination approaches against the HBV. Thus, strong primary Th cell responses against the HBV core (HBc) and the Borrelia burgdorferi control antigen were induced by transfer of antigen-loaded dendritic cells together with autologous PBMC from HBV-naive donors as well as by vaccination with high doses of antigen or a DNA plasmid encoding for HBcAg. Moreover, primary peptide-specific CTL responses against the immunodominant epitope HBc(18 - 27) were induced by HBc particle or DNA vaccination of chimera engrafted with HBV-naive PBMC. Finally, strong HBc-specific Th cell and antibody responses were induced by HBc or DNA vaccination of mice reconstituted with PBMC from a chronic HBV patient. Thus, since HBc represents the immunodominant antigen in self-limited HBV infection, HBc particles or DNA vectors are good candidates for therapeutic vaccination, that will be further studied in our model and clinical studies.

Animals↗

PubMed2005

A novel model of drug hapten-induced hepatitis with increased mast cells in the BALB/c mouse.

Clinical evidence suggests that idiosyncratic hepatitis following administration of halogenated volatile anesthetics is mediated by autoimmune responses. No murine model to study mechanisms of anesthetic-induced or any other form of drug-induced idiosyncratic hepatitis exists. Anesthetics are believed to trigger hepatitis by covalently linking a trifluoroacetyl (TFA) chloride hapten to hepatic proteins, forming haptenated self-proteins. To test this hypothesis, we developed a hapten-induced model of hepatitis by immunization with syngeneic S100 liver proteins covalently coupled to TFA (TFA-S100). We found that TFA-S100 induced hepatitis was more severe than disease induced by S100 plus adjuvants or by the adjuvant alone and was characterized by neutrophil, mast cell, and eosinophil infiltration. TFA-specific IgG1 antibodies directly correlated with hepatitis, whereas S100 autoantibodies did not. TNF-alpha, IL-1beta, and IL-6 released from splenocytes collected 2 weeks after TFA-S100 inoculation were increased resembling the elevated serum cytokines reported in patients with autoimmune hepatitis (AIH). Three weeks after inoculation, the peak of hepatitis, we noted decreased numbers of Kupffer cells and lower levels of IL-6 and IL-10 in the liver, cytokines produced by Kupffer cells. This is the first report, to our knowledge, of a hapten-induced model of hepatitis with immune and autoimmune features.

Anesthetics, Inhalation↗

PubMed1992

Effects of rufloxacin in Salmonella typhimurium infection in mice.

This study was undertaken to investigate the efficacy of rufloxacin, a new quinolone which is interesting due to its pharmacokinetics characterized by a long plasma half-life, in the treatment of systemic salmonella infections in the mouse typhoid model. Innately susceptible BALB/c and resistant CBA mice were used to investigate the efficacy of rufloxacin in controlling systemic salmonella infections when given for brief or prolonged periods. The present study shows that rufloxacin is not only very effective on both mouse strains, but can completely eradicate the salmonellae from livers and spleens when given early in the infection of CBA resistant mice.

Animals↗

PubMed2000

Litomosoides sigmodontis: dynamics of the survival of microfilariae in resistant and susceptible strains of mice.

Litomosoides sigmodontis in the BALB/c mouse is the only model of filariasis which allows the observation of the complete development in an immunocompetent mouse. In this study, we injected microfilariae (mf) intravenously, as well as into the pleural cavity, the site of natural release of mf from adult female worms, and followed the kinetics of elimination within the host. In susceptible BALB/c mice, mf circulated at high levels in the blood. In contrast, in C57BL/6 mice, which are refractory to full development, mf were eliminated rapidly from the peripheral blood. However, 6 days after intrapleural injection, viable larvae could be found in the pleural cavity and lung capillaries of both susceptible and resistant strains. The numbers of mf in the pleural cavity and lung capillaries in individual mice were significantly correlated, but not dependent on strain or peripheral microfilaraemia. Thus, although C57BL/6 mice showed enhanced production of nitric oxide by pleural exudate cells and a faster change in the numbers of circulating leukocytes after injection, rapid killing of mf by cell or nitric oxide-mediated mechanisms were not the reason for the different outcome. Furthermore, 3 h after iv injection, only a small percentage of mf could be recovered from the peripheral circulation, indicating the presence of a reservoir for mf containment. In conclusion, injected mf showed disparate dynamics of persistence within susceptible and resistant hosts, which is similar to the disparate outcome of natural infections with L. sigmodontis. This difference became obvious within 1 day after injection. The lung capillary system plays obviously a crucial part in regulation of microfilaremia. Our model also provides a possible means to explain frequent cases of occult infections in human filariasis.

Animals↗

PubMed2006

Chemoprotection effect of multidrug resistance 1 (MDR1) gene transfer to hematopoietic progenitor cells and engrafted in mice with cancer allows intensified chemotherapy.

Increasing the proportion of bone marrow cells expression human multidrug resistance (MDR) 1 gene to prevent or circumvent bone morrow toxicity from chemotherapy agent is a high priority of dose intensification protocols. In this study, we have used a BALB/c mouse tumor-bearing model to investigate the chemoprotection effect of MDR1 gene by transfecting retroviral vectors containing and expressing the MDR gene in vivo. Hematopoietic progenitor cells served as a target of MDR1 gene transfer by the mediation of retrovirus vector and engrafted into the BALB/c mice with 60Co-gamma ray exposure in advance. Doxorubicin (5, 10, and 20 mg/kg) suppressed tumor growth of the xenograft significantly in dose-dependence mode if supported by suitable peripheral WBC. WBCs count revealed that the mice that had received gene-transduced cells showed a significant increase in WBCs count compared with their gene-transduced-naive counterparts. The function and expression of MDR1 gene were detected by flow cytometry, RT-PCR and immunohistochemistry (IC) method. MDRl mRNA expression could be detected in BM. Spleens contained measurable amounts of MDRl mRNA. Tail vein blood and tumor tissue detected MDRl DNA but no MDRl mRNA expression. FACS analysis of infected BM cells obtained 6 weeks later showed high levels of P-gp function. Based on these results we conclude that cytostatic drug resistance gene therapy may provide some degree of chemoprotection so can increase the chemotherapy dose to kill tumor cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Presbyacusis and calcium-binding protein immunoreactivity in the cochlear nucleus of BALB/c mice.

The BALB/c mouse is an established model for the early development of sensorineural hearing loss, and is homozygous for the Ahl allele (age-related hearing loss). The present study was designed to determine how auditory peripheral pathology influences calcium-binding protein immunoreactivity in the cochlear nucleus in aged BALB/c mice. To address this issue the loss of hair cells, spiral ganglion neurons (SGN), and neurons in the dorsal (DCN) and posteroventral (PVCN) cochlear nucleus of BALB/c mice at 1 and 24 months of age were quantified using CAST stereological methods. These values were then compared to the percent increase in immunopositive calcium-binding proteins in the cochlear nucleus. By 24 months of age there was a near complete loss of all outer hair cells (OHC). The inner hair cell (IHC) loss was near complete in the more apical and basal regions, while in the mid-regions approximately 50% were missing. The SGN in the apical and middle turns show a 20% loss (re: 1 month) and the basal turn up to 80% loss. A statistically significant decrease in the density of DCN and PVCN neurons (25%) was found at 24 months of age compared to the one month old animals. The percentage of parvalbumin and calretinin positive neurons in the DCN and the PVCN in relation to the density of Nissl stained neurons showed significant increases at 24 months compared to the 1 month old animals. We also determine the relationship between peripheral pathology and the percent increase in calcium-binding protein immunoreactivity. In the DCN, the percent increase of calretinin and parvalbumin was correlated to the loss of SGN, IHCs and OHCs. In the PVCN, parvalbumin was correlated to SGN, IHC, and OHC loss. The percent increase in calbindin immunoreactivity was not correlated to any peripheral pathology. The data here suggest a percent increase in calcium-binding protein immunoreactivity in the cochlea nucleus in the 24 month old mice may reflect an endogenous protective strategy that is designed to counteract calcium overload that is prominent during aging and degeneration. These results will be valuable for understanding the relationship among the peripheral and central auditory system in a model demonstrating a rapidly progressive presbyacusis.

Aging↗

PubMed2006

An Argentine equine herpesvirus strain with special restriction patterns protect mice challenged with a pathogenic strain.

Equine herpesvirus 1 (EHV-1) was first isolated in Argentina in 1979. This strain SPv has special restriction patterns, but a previous study demonstrated that SPv did not modify its growth in cell culture. In addition, it showed low virulence in the mouse respiratory model consistently with results found in female BALB/C at different state of gestation. This study evaluates in a mouse respiratory model, if primary infection with SPv strain protects animals from subsequent challenge with a pathogenic strain. Body weight loss was not observed in mice intranasally inoculated with SPv strain and challenged with HH1 Japanese strain. The SPv primary infection does not completely prevent clinical presentation by HH1 infection but the SPv inoculated animals recovered more quickly, with less intense and less persistent histological lesions. The challenge infection caused a rapid and prolonged increase in anti-EHV-1 antibodies in the mice previously infected with SPv, along with a more rapid reduction of viral titres in lungs. In this work it was demonstrated that this EHV-1 strain constitute a good immunogen. These results show that this SPv strain could be considered to produce an EHV-1 vaccine.

Animals↗

PubMed1997

In vivo toxicity, pharmacokinetics, and antileukemic activity of TXU (anti-CD7)-pokeweed antiviral protein immunotoxin.

We evaluated the TXU (anti-CD7)-pokeweed antiviral protein (PAP) immunotoxin in both murine and nonhuman primate models. TXU-PAP caused dose-limiting cardiac toxicity in BALB/c mice. In a SCID mouse model of invariably fatal human T-lineage acute lymphoblastic leukemia (ALL), TXU-PAP therapy resulted in a marked improvement of leukemia-free survival without any side effects. Whereas 100% of control mice treated with PBS, unconjugated TXU antibody, or B43-PAP (an immunotoxin that does not react with T-lineage ALL cells) died of disseminated human leukemia within 80 days (median survival, 37 days), 80 +/- 13% of SCID mice treated with 15 microgram of TXU-PAP (median survival, >120 days) and 100% of mice treated with 30 microgram of TXU-PAP (median survival, > 120 days) remained alive and free of leukemia for >120 days. In cynomolgus monkeys, TXU-PAP showed favorable pharmacokinetics with an elimination half-life of 8.1-8.7 h. The monkeys treated with TXU-PAP at dose levels of 0.05 mg/kg/day x 5 days and 0.10 mg/kg/day x 5 days tolerated the therapy very well, without any significant clinical compromise or side effects, and at necropsy, no gross or microscopic lesions were found. This study provides a basis for further evaluation of TXU-PAP as an investigational biotherapeutic agent in the treatment of T-lineage ALL.

Animals↗

PubMed2000

Therapeutic efficacy of anti-Lewis(y) humanized 3S193 radioimmunotherapy in a breast cancer model: enhanced activity when combined with taxol chemotherapy.

Monoclonal antibody therapy may provide new treatment options in the management of metastatic breast cancer by selectively targeting tumors and producing a therapeutic effect, by delivering radiation or other toxins directly to tumor cells, or by producing an intrinsic immune inflammatory response. The effect of 131I-labeled humanized anti-Lewis(y) monoclonal antibody 3S193 (hu3S193) was compared with that of placebo and radiolabeled huA33 control antibody in a series of radioimmunotherapy experiments in a MCF-7 xenografted BALB/c nude mouse breast cancer model. The maximum tolerated dose of 131I-labeled antibody occurred at 200 microCi/mouse, at which dose level three of six mice that received 131I-hu3S193 showed significant tumor growth inhibition in contrast to no responses in the comparable 131I-huA33 control treatment arm. Breast cancer is an ideal model to test the efficacy of combined modalities given its known sensitivity to both radiotherapy and chemotherapy. The synergy between radioimmunotherapy and chemotherapy was therefore also explored using a combination of 131I-labeled hu3S193 antibody and Taxol using subtherapeutic doses of each agent. The combination of Taxol and 100 microCi of 131I-hu3S193 produced significant tumor inhibition in 80% of mice, whereas no responses were seen with either treatment modality alone or the combination of Taxol and 131I-huA33. These results support a potential therapeutic role of radiolabeled hu3S193 in the treatment of breast cancer, including combination therapy with Taxol, and warrants further investigation of this promising new agent.

Adenocarcinoma↗

PubMed2005

PREDBALB/c: a system for the prediction of peptide binding to H2d molecules, a haplotype of the BALB/c mouse.

PRED(BALB/c) is a computational system that predicts peptides binding to the major histocompatibility complex-2 (H2(d)) of the BALB/c mouse, an important laboratory model organism. The predictions include the complete set of H2(d) class I (H2-K(d), H2-L(d) and H2-D(d)) and class II (I-E(d) and I-A(d)) molecules. The prediction system utilizes quantitative matrices, which were rigorously validated using experimentally determined binders and non-binders and also by in vivo studies using viral proteins. The prediction performance of PRED(BALB/c) is of very high accuracy. To our knowledge, this is the first online server for the prediction of peptides binding to a complete set of major histocompatibility complex molecules in a model organism (H2(d) haplotype). PRED(BALB/c) is available at http://antigen.i2r.a-star.edu.sg/predBalbc/.

Animals↗

PubMed1994

Photoimmunotherapy and biodistribution with an OC125-chlorin immunoconjugate in an in vivo murine ovarian cancer model.

Photodynamic therapy (PDT) is an experimental approach to the treatment of neoplasms in which photosensitisers (PSs) accumulated in malignant tissues are photoactivated with appropriate wavelengths of light. The target specificity of PSs may be improved by linking them with carrier macromolecules such as monoclonal antibodies (MAbs). OC125 is a murine MAb that recognises the antigen CA 125, which is expressed on 80% of non-mucinous ovarian tumours. A chlorin derivative conjugated to OC125 was shown to be selectively phototoxic to ovarian cancer and other CA 125-positive cells in vitro and ex vivo. We now report in vivo studies using an ascitic Balb/c nude mouse ovarian cancer model. Ascites was induced by intraperitoneal injection of cells from the human ovarian cancer cell line NIH:OVCAR3. Six weeks after injection, when the animals had developed ascites, biodistribution studies were carried out by injecting the immunoconjugate (IC) or free PS intraperitoneally and sacrificing the animals at 3, 6, 12, 24, 48, 72 and 168 h later. The PS was quantitated by extraction and fluorescence spectroscopy. For both the IC and free PS, peak tumour concentrations were reached at 24 h; however, the absolute concentrations for the IC were always higher (2- to 3-fold) than the free PS. Tumour to non-tumour ratios at 24 h for the IC were 6.8 for blood, 6.5 for liver, 7.2 for kidney, 5.7 for skin and 3.5 for intestine. Evaluation of viable tumour cells in ascites following in vivo PDT with a single light exposure demonstrated a dose-dependent relationship with fluence and IC concentration. However, there was significant treatment-related toxicity at all fluences. With multiple low-dose treatments, the percentage of viable tumour cells was also significantly reduced and there were no treatment-related deaths. These data suggest that, while photoimmunotherapy remains promising as a new treatment modality for ovarian cancers, careful quantitative dosimetry of both IC and light may need to be combined with multiple treatments (as with radiation therapy and chemotherapy) to control malignant disease yet maintain acceptable toxicity in vivo.

Animals↗

PubMed2000

Enhanced T cell cytokine gene expression in mouse airway obliterative bronchiolitis.

BACKGROUND: Obliterative bronchiolitis (OB), chronic allograft rejection of the lung, is a major cause of morbidity and mortality after lung transplantation. Previous studies using the heterotopic mouse trachea model of chronic airway rejection have shown a T cell infiltrate composed of CD4+ and CD8+ T cells. The goal of these experiments was to characterize the pattern of T lymphocyte cytokines during chronic airway rejection using the heterotopic mouse trachea model. METHODS: Isografts (BALB/c into BALB/c) and allografts (BALB/c into C57BL/6) were implanted into cyclosporin-treated animals and harvested 2, 4, 6, and 10 weeks posttransplant. Cytokine mRNA expression in these grafts was determined using reverse transcription polymerase chain reactions. Expression of Th1 cytokines, interleukin- (IL) 2 and gamma-interferon, and Th2 cytokines, IL-4, and IL-10 were analyzed, as well as the cytotoxic lymphocyte product granzyme B and expressed relative to beta-actin gene expression. RESULTS: In allografts, expression of IL-2 (P=0.002), gamma-interferon (P=2x10(-6)), granzyme B (P=0.003), IL-4 (P=0.06), and IL-10 (P=8x10(-6)) were 2- to 10-fold higher compared to isografts throughout the time-course of graft injury. Th1 and cytotoxic lymphocyte gene expression were increased to a greater extent than Th2 cytokines in allografts compared with isografts, and both Th1 and Th2 cytokine gene expression persisted at 6-10 weeks. CONCLUSIONS: These data suggest that Th1, Th2, and cytotoxic lymphocyte subtypes all contribute to the development of obliterative bronchiolitis in the heterotopic mouse trachea model. Efforts to reduce the development of obliterative bronchiolitis may require the antagonism of multiple T cell pathways.

Animals↗

PubMed2004

An animal model for the tickborne flavivirus--Omsk hemorrhagic fever virus.

The tickborne encephalitis (TBE) serocomplex of flaviviruses consists primarily of viruses that cause neurologic disease; these viruses include Omsk hemorrhagic fever virus (OHFV), a virus that is genetically related to other TBE serocomplex viruses but that circulates in an ecologically distinct niche and causes markedly different human disease. The objective of this study was to examine a potential small-animal model for OHFV and to compare the pathology of infection with that of the neurotropic tickborne flavivirus, Powassan virus (POWV). POWV-infected BALB/c mice demonstrated typical arboviral encephalitis, characterized by paresis and paralysis before death, and viral infection of the cerebrum, characterized by inflammation and necrosis. In contrast, lethal OHFV infection did not cause paralysis or significant infection of the cerebrum but showed marked involvement of the cerebellum. Distinct pathological results in the spleens suggest that the immune response in OHFV-infected mice is different from that in POWV-infected mice. This study demonstrates a clear pathological difference between OHFV-infected mice and POWV-infected mice and supports the use of the BALB/c mouse as a disease model for OHFV.

Animals↗