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Results for “BALB/c mouse model”

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PubMed1996

Efficient targeting of the IL-4 gene in a BALB/c embryonic stem cell line.

Embryonic stem (ES) cell lines have been derived from the inner cell mass of day 3.5 blastocysts of the inbred mouse strain BALB/cJ. Twenty-three lines were karyotyped and three were selected for injection into C57BL/6J host blastocysts. Two of the three lines, BALB/c-I and BALB/c-IV, produced germ-line chimaeras. The suitability of the BALB/c-I line for gene targeting experiments was tested by transfecting a targeting construct for the interleukin-4 (IL-4) gene. Transfected BALB/c-I cells exhibited efficient homologous recombination of the targeting vector and transmitted the induced mutation through the germline. This newly-characterized BALB/c-ES cell line thus provides an alternative to the traditional 129-derived and the recently described C57BL/6 embryonic stem cell lines, and will be useful in disrupting genes involved in the immune system. Furthermore, the genetically pure BALB/c IL-4 deficient mice will aid in studying the role of IL-4 in several infectious disease models in which the BALB/c mouse is a susceptible strain.

Animals↗

PubMed2006

Immunogenicity of Mycobacterium ulcerans Hsp65 and protective efficacy of a Mycobacterium leprae Hsp65-based DNA vaccine against Buruli ulcer.

Buruli ulcer, a disease caused by Mycobacterium ulcerans, is emerging as an increasingly important cause of morbidity throughout the world, for which surgery is the only efficient treatment to date. The aim of this work was to identify potential vaccine candidates in an experimental model of mouse infection. In BALB/c mice infected with M. ulcerans subcutaneously, Hsp65 appeared to be an immunodominant antigen eliciting both humoral and cellular responses. However, vaccination of mice with a DNA vector encoding Mycobacterium leprae Hsp65 only poorly limited the progression of M. ulcerans infection. In contrast, a substantial degree of protection was conferred by subcutaneous vaccination with BCG, suggesting that BCG antigens that are conserved in M. ulcerans, such as TB10.4, the 19 kDa antigen, PstS3 and Hsp70, may be interesting to consider as subunit vaccines in future prospects.

Animals↗

PubMed1997

Growth of P511 mastocytoma cells in BALB/c mouse brain elicits CTL response without tumor elimination: a new tumor model for regional central nervous system immunity.

We have developed a murine model to explore the tumor-specific CTL response in the immune-privileged central nervous system using P511 mastocytoma cells. Three strains with varying degrees of histocompatibility to P511 cells (CD-1, allogeneic; BALB/c, minor histoincompatible; DBA/2, syngeneic) received tumor cells (10(4)) into the putamen 7 days after cannula implantation, when the blood-brain barrier was functionally intact. Without exception, tumor formed reproducibly by day 7 in all strains. Tumor rejection occurred in CD-1 but not in BALB/c and DBA/2 mice. Using a flank injection site, both CD-1 and BALB/c, but not DBA/2 mice, ultimately rejected flank tumors. Analysis of tumor-specific CTL in BALB/c spleens revealed that P511 administration into brain or flank elicited similar responses: no fully activated CTL were detectable but a significantly expanded population of nonkilling precursors of CTL (pCTL) were present. A P511 cell-specific pCTL population was also identified at the brain tumor site 14 days post-tumor introduction, indicating that pCTL, generated in the periphery, traffic to the tumor site in brain. These data indicate that failure to reject tumor in brain is neither due to lack of afferent stimulation nor to inability of peripheral effectors (P511 cell-specific pCTL) to reach the tumor site. We hypothesize that these effector cells are prevented from developing into fully activated CTL by conditions within the central nervous system microenvironment that down-regulate CTL development.

Animals↗

PubMed1997

Cytotoxic T lymphocyte responses to wild-type and mutant mouse p53 peptides.

Cytotoxic T lymphocytes (CTL) recognize peptides presented at the cell surface in association with major histocompatibility complex (MHC) class I molecules. The finding that peptides binding to MHC class I molecules share common amino acid motifs renders feasible the selection of antigenic peptides by simply scanning protein sequences, and thus, provides the possibility of inducing CTL to pre-defined specificities. Tumor cells possess antigens known to generate MHC class I-restricted CD8+ CTL responses. Thus, these antigens represent good targets to induce tumor-specific immunity. Among these antigens, the p53 tumor suppressor gene product is an attractive candidate for cancer immunotherapy. Mutations in the p53 gene have been found to be very frequently associated with a malignant transformation and often lead to p53 protein overexpression. Thus, we investigated the possibility of inducing CTL to wild-type or mutant p53 peptides in a BALB/c (H-2d) mouse model. Peptides possessing the H2-Kd binding motif were selected and tested for binding to the H-2Kd molecules in vitro. Synthetic peptides p53(122-130) wild-type or "mutant" (Lys --> Glu substitution at position 129) were shown to be the best binder peptides and were tested for their immunogenicity in mice. H-2Kd-restricted p53-specific CD8+ CTL were generated following immunization of mice with either wild-type (wt) p53(122-130) or mutant (mut) p53(122-130) (E129) peptides. Only low-affinity CTL can be obtained by immunization with the wt sequence. In contrast, CTL elicited with the mut peptide recognized the mut sequence at a 10-100-fold lower concentration. This indicates that CTL elicited with the mut peptide recognized the mut sequence very efficiently, whereas the wt sequence is poorly recognized, if at all. Taken together, these results thus suggest that p53-specific tumor immunotherapy may be successful only if the mutated protein is taken into consideration.

Animals↗

PubMed1990

Two-dimensional gel analysis of polypeptides from normal, preneoplastic and neoplastic mouse mammary tissues.

High-resolution two-dimensional polyacrylamide gel electrophoresis (PAGE) was employed to reveal tumor-associated polypeptide changes, using the BALB/c C4 line mouse mammary model system, for which phenotypic and immunogenic alterations accompanying tumor progression are well defined. In the first set of experiments, polypeptide patterns from 20 micrograms whole tissue lysates of normal mammary gland, C4 preneoplastic hyperplastic alveolar nodule outgrowth (HAN) and spontaneous tumor from C4 HAN were compared. In order to normalize for differential cellularity and extracellular protein content in the whole tissues, our analysis included polypeptide patterns from serum, increased concentration of protein from whole normal mammary gland, and primary cultures of epithelial cells from normal gland, HAN and tumor. Using a computer-based image-analysis system, 90 polypeptides were identified in C4 tumor that were absent in C4 HAN, normal mammary gland and serum. None of the 90 polypeptides could be shown to represent a definite qualitative change in the protein composition of tumor epithelium as they were found to be either present in a higher concentration of protein from whole normal gland, or present in the primary epithelial culture from HAN, or absent in the primary epithelial culture from tumor. Conversely in the second set of experiments, when epithelial cultures were used as the starting point for comparisons to locate tumor-associated polypeptides, none of the 15 polypeptides that were present in cultures from three different tumors, and absent in the culture from normal mammary gland was specific to C4 tumor, as they were present in whole tissues of normal gland. Thus our experimental approach detected significant quantitative but no qualitative polypeptide changes in whole tumor tissue, or in tumor-derived epithelial cell cultures. This finding may reflect the limitations of the two-dimensional PAGE method, and warrants caution in the use of such gel analysis alone to identify tumor-associated proteins.

Animals↗

PubMed2001

Liver metastasis following pneumoperitoneum with different gases in a mouse model.

BACKGROUND: The validity of using CO2 in laparoscopic tumor surgery has not yet been established. To address this question, we investigated the growth of liver metastases following insufflation with different gases in a mouse laparoscopy model. METHODS: Male BALB/C mice inoculated intraportally with colon 26 cells were randomized to undergo pneumoperitoneum with CO2 (n = 16), helium (n = 16), argon (n = 16), or air (n = 17), or to act as controls without insufflation (n = 17). RESULTS: The growth of cancer nodules on the liver 14 days after surgery was greater in mice following insufflation with CO2 (p < 0.01), helium (p < 0.01), argon (p = 0.01), and air (p = 0.07) than in control mice. No significant differences were found between the four insufflation groups in the growth of liver metastases. CONCLUSION: These results suggest that insufflation plays an important role in the development of liver metastases but that the choice of gas may not affect their growth.

Analysis of Variance↗

PubMed2004

Nasal immunization of mice with a rotavirus DNA vaccine that induces protective intestinal IgA antibodies.

DNA vaccination using a plasmid encoding the rotavirus inner capsid VP6 has been explored in the mouse model of rotavirus infection. BALB/c mice were immunized with a VP6 DNA vaccine by the intramuscular, nasal and oral routes. VP6 DNA vaccination by the nasal and oral routes induced the production of anti-VP6 IgA antibodies by intestinal lymphoid cells. Intramuscular DNA injection stimulated the production of serum anti-VP6 IgG but not serum anti-VP6 IgA antibodies. Protection against shedding of rotaviruses in stools after oral challenge with the murine EDIM rotavirus strain was investigated in the immunized mice. A significant reduction in the level of rotavirus antigen shedding was demonstrated in those mice immunized at mucosal surfaces, both orally and nasally, with the VP6 DNA vaccine. Intramuscular DNA immunization, which elicited serum anti-VP6 IgG responses but not virus-specific intestinal IgA antibodies, did not provide significant protection against rotavirus challenge.

Administration, Intranasal↗

PubMed2006

Recombinant adenovirus expressing GP5 and M fusion proteins of porcine reproductive and respiratory syndrome virus induce both humoral and cell-mediated immune responses in mice.

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important contagious agents of swine in the world. PRRSV infection poses a challenge to current vaccination strategies. In this study, three replication-defective adenovirus recombinants were developed as potential vaccine against PRRSV in a mouse model. Three groups of BALB/c mice (24 mice per group) were inoculated subcutaneously twice at 2-week intervals with the recombinants expressing PRRSV GP5 (rAd-GP5), M (rAd-M), and M-GP5 fusion protein (rAd-M-GP5). Two additional groups were injected with wild-type adenovirus (wtAd) or PBS as control. The results showed that the mice inoculated with recombinant adenoviruses developed PRRSV-specific antibodies, cellular immune response by 2 weeks post second inoculation. However, only mice immunized with recombinant adenovirus rAd-M-GP5 developed significantly higher titers of neutralizing antibodies to PRRSV and produced stronger lymphocyte proliferation responses compared to mice immunized with rAd-M or rAd-GP5 alone. It was also found that mice immunized with rAd-M-GP5 were primed for significant higher levels of anti-PRRSV CTL responses than mice immunized with rAd-M. Mice receiving rAd-GP5 also mounted PRRSV-specific response, but levels were lower. It suggested that the recombinant adenovirus expressing M-GP5 fusion protein might be an attractive candidate vaccine to be tested for preventing PRRSV infection.

Adenoviridae↗

PubMed2000

Polyglutamation of antifolates is not required for induction of extracellular release of adenosine or expression of their anti-inflammatory effects.

Methotrexate (MTX) exerts an anti-inflammatory effect, reportedly by enhancing the release of adenosine, through an accumulation of 5-amino-4-imidazolecarboxamide ribonucleotide (AICAR). To examine the role of polyglutamation in promoting anti-inflammatory effects by antifolates, we tested whether a new antifolate designed to be resistant to intracellular polyglutamation (MX-68) exhibited anti-inflammatory effects and stimulated adenosine release. Both MX-68 and MTX (at concentrations greater than 0.1 microM) increased the release of adenosine from Daudi cells in vitro. Inhibition of AICAR synthesis suppressed adenosine release by MX-68 and MTX. The anti-inflammatory effects of antifolates were estimated using the murine air pouch model, in which a BALB/c mouse was intraperitoneally injected with MX-68 or MTX once a week for 3 weeks. MX-68 (0.5 mg kg(-1) week(-1)), as well as MTX, inhibited infiltration of leukocytes into the air pouch. This inhibitory effect was suppressed in the presence of an adenosine A(2) receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX). These results suggest that MX-68, like MTX, exerts anti-inflammatory effects through the accumulation of AICAR and release of adenosine. These results suggest that polyglutamation of antifolate is not required for expression of anti-inflammatory effects.

2-Aminoadipic Acid↗

PubMed2002

Infection with influenza a virus leads to flu antigen-induced cutaneous anaphylaxis in mice.

It is well established, that viral infections may trigger urticaria or allergic asthma; however, as viral infections induce T helper 1 polarized responses, which lead to the inhibition of T helper 2 cell development, the opposite would be plausible. We wanted to investigate how viral infections may mediate allergic symptoms in a mouse model; therefore, we infected BALB/C mice with influenza A virus intranasally. Histologic analyses of lung sections and bronchoalveolar lavages were performed. In addition, cells from the mediastinal lymph nodes were restimulated in vitro to analyze which types of cytokines were induced by the flu infection. Furthermore, flu-specific antibody titers were determined and local anaphylaxis was measured after rechallenge with flu antigen. We found that airways inflammation consisted predominately of macrophages and lymphocytes, whereas only a few eosinophils were observed. interferon-gamma but no interleukin-4 and little interleukin-5 could be detected in the culture supernatants from in vitro restimulated T cells from the draining lymph nodes. The antibody response was characterized by high levels of virus-specific IgG2a, IgG2b, and IgG1 and, surprisingly, low levels of virus-specific IgE antibodies. Interestingly, flu-infected mice developed active and passive cutaneous anaphylaxis after rechallenge with flu-antigen. As the passive cutaneous anaphylaxis reaction persisted over 48 h and was significantly lower after passive transfer of the serum, which was IgE depleted, local anaphylaxis seemed to be mediated predominately by specific IgE antibodies. Taken together, our results demonstrate that mice infected with flu virus develop virus-specific mast cell degranulation in the skin. Our results may also have implications for the pathogenesis of urticaria or other atopic disorders in humans.

Anaphylaxis↗

PubMed2005

Effect of gamma irradiation on the osteoinductivity of morphogenetic protein extract from reindeer bone.

BACKGROUND: Bone morphogenetic proteins (BMPs), which are capable of stimulating the production of new bone, must be sterilized before preclinical and clinical use to reduce the risk of infections and associated complications. In this study, we investigated the effects of gamma sterilization on the osteoinductivity of native reindeer BMP extract in the Balb/C mouse thigh muscle pouch model. METHODS: 5 mg of native reindeer BMP extract and 5 mg of bovine serum albumin were administered separately either in gelatine capsules or mixed with gelatine as injections. The dose of gamma irradiation was 4.1 Mrad. Unsterile capsules and injections served as controls. New bone formation was evaluated based on the incorporation of Ca45 and also radiographically 3 weeks after implantation. RESULTS: Albumin-containing implants and injections did not induce new bone formation, as monitored in radiographs. Gamma sterilization did not reduce the osteoinductivity of native BMP extract in capsules, but a significant decrease in osteoinductivity--measured as area (50%) and Ca45 incorporation of new bone (27%)--was seen after injection. Gamma sterilization had no effect on the optical density of new bone induced by native BMP extract administered in capsules or by injection. INTERPRETATION: We conclude that, as gamma irradiation did not reduce the osteoinductivity of reindeer BMP extract in gelatine capsules, this method appears to be suitable for sterilization of BMPs to be given in capsule form. Native reindeer BMP extract was more sensitive to irradiation in soluble collagen (gelatine) than BMP in gelatine capsules. This finding must be given serious consideration regarding treatment of patients, but the remaining activity may be sufficient for the induction of bone formation in preclinical and clinical situations.

Animals↗

PubMed1990

Beta-lactam antibiotics (aztreonam, ampicillin, cefazolin and ceftazidime) in the control and eradication of Salmonella typhimurium in naturally resistant and susceptible mice.

This study was undertaken to investigate the efficacy of different beta-lactam antibiotics in the treatment of systemic salmonella infections in the mouse typhoid model. Innately susceptible BALB/c (Itys) and resistant CBA (Ityr) mice were used to investigate the efficacy of one monocyclic (aztreonam) and three bicyclic (ampicillin, cefazolin, ceftazidime) beta-lactam antibiotics in controlling systemic salmonella infections when given for brief or prolonged periods. The present study confirms and amplifies earlier reports on ampicillin therapy, demonstrates marked differences in the efficacy of the different antibiotics and shows that aztreonam is not only very effective but can completely eradicate the salmonellae from the RES when given early in the infection.

Ampicillin↗

PubMed2003

Ultrafine carbon black particles enhance respiratory syncytial virus-induced airway reactivity, pulmonary inflammation, and chemokine expression.

Exposure to particulate matter (PM) may exacerbate preexisting respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), bronchitis, and pneumonia. However, few experimental studies have addressed the effects of PM on lower respiratory tract (LRT) viral infection. Respiratory syncytial virus (RSV) is a major etiological agent for LRT infections in infants, the elderly, and the immunocompromised and may lead to chronic wheezing and the development of asthma in children. In this study, we examined the effects of carbon black (CB) on RSV-induced pulmonary inflammation, chemokine and cytokine expression, and airway hyperresponsiveness in a mouse model of RSV. Female BALB/c mice were instilled via the trachea (i.t.) with 1 x 106 plaque forming units (pfu) RSV or with uninfected culture media. On day 3 of infection, mice were i.t. instilled with either 40 micro g ultrafine CB particles or with saline. End points were examined on days 4, 5, 7, and 14 of RSV infection. Viral titer and clearance in the lung were unaffected by CB exposure. Neutrophil numbers were elevated on days 4 and 7, and lymphocyte numbers were higher on days 4 and 14 of infection in CB-exposed, RSV-infected mice. CB exposure also enhanced RSV-induced airway hyperresponsiveness to methacholine, bronchoalveolar lavage (BAL) total protein, and virus-associated chemokines monocyte chemoattractant protein (MCP-1), macrophage inflammatory protein (MIP-1 alpha), and regulated upon activation, normal T cell expressed and secreted (RANTES). MIP-1 alpha mRNA expression was increased in the alveolar epithelium, where ultrafine particles deposit in the lung. These data demonstrate a synergistic effect of ultrafine CB particles on RSV infection, and suggest a potential mechanism for increased respiratory infections in human populations after PM exposure.

Animals↗

PubMedDate not supplied

Differences in IgM synthesis to gut bacterial peptidoglycan polysaccharide after burn injury and gut ischemia.

Both burn injury and intestinal ischemia have been proven to induce bacterial translocation from the gut. It is still unknown, however, whether the bacteria induces immune response in these different models. To assess this, we measured in vitro IgM synthesis to peptidoglycan polysaccharide (PGPS), a ubiquitous gut bacterial antigen, after burn injury or gut ischemia-reperfusion in a mouse model. Eighty-five BALB/c mice were divided into four groups. Gut ischemia was produced by placing a vessel loop around the superior mesenteric artery at celiotomy (group Isc; n = 31). After 45 minutes, the abdomen was reopened, and the vessel loop removed. All animals had visible gut ischemia. Control mice (group Isc-C; n = 15) underwent two sham operations. Burn injury was 25% body surface area full-thickness to the dorsum (group B; n = 27). Another control group (B-C; n = 12) was also used. Animals were euthanized 24 hours after recirculation or 5 days after the burn injury. All spleens were removed, and cell suspensions prepared. Cells were cultured in 2.5 micrograms/ml lipopolysaccharide for 5 days, and anti-PGPS IgM level in the supernatant was measured by an enzyme-linked immunosorbent assay. Intestinal ischemia produced a significant rise in in vitro anti-PGPS IgM synthesis per 10(5) lymphocytes, which is the principal immunoglobulin response to infection. However, anti-PGPS IgM in mice after burn injury was significantly decreased. This decreased IgM synthesis after burn injury compared to gut ischemia may represent continued immune impairment from the burn wound, and may account for organ dysfunction related to bacterial translocation after burn injury.

Animals↗

PubMed1995

Enhanced type 2 and diminished type 1 cytokines in neonatal tolerance.

We examined the cytokine profiles associated with tolerance and rejection using the mouse model of neonatal tolerance. BALB/c mice primed with CAF1 splenocytes during the neonatal stage showed increased A/J skin graft survival of > 60 days and failed to develop anti-A/J cytotoxic responses, but rejected third-party C57BL/6 grafts. Lymph node cells that drained A/J grafts on neonatal-primed mice produced allospecific immune cytokine responses characterized by high IL-4 and low IFN-gamma levels. In contrast, lymph node cells that drained either rejected third-party grafts or rejected A/J grafts placed on adult controls produced less IL-4 and more IFN-gamma. Tolerogen-specific immune responses from neonatal-primed mice made up to 100 times higher IL-4 to IFN-gamma ratios than did controls. Alloantigen priming during the immediate neonatal stage induced constitutive expression of IL-4 mRNA in the spleen without IFN-gamma mRNA, whereas alloantigen stimulation during adulthood induced the opposite pattern. IL-4 production from neonatal primed mice was confined to the CD4 population. The altered cytokine profile of enhanced IL-4/IFN-gamma in neonatal primed mice persisted for up to 12 weeks after priming in in vitro secondary MLR assays, which suggests that the initial timing of antigen stimulation critically influenced CD4 maturation. The results support a model of immunoredirection as a mechanism of tolerance and provide rationale for examining the therapeutic use of cytokines in transplantation.

Aging↗

PubMed2000

Comparison between tacrolimus and cyclosporine as immunosuppressive agents compatible with tolerance induction by CD4/CD8 blockade.

BACKGROUND: Donor-specific tolerance can be induced in mice by transient antibody blockade of the CD4 and CD8 co-receptors of T cells. To evaluate the potential application of CD4/CD8 blockade in the clinic, we have asked if either tacrolimus or cyclosporine counteract the tolerogenic process. METHODS: Using the fully mismatched mouse cervical heart transplant model, BALB/c (H2d) to CBA (H2k), the experimental groups were (i) no therapy, (ii) tacrolimus (1 mg/kg, i.p., daily, days 0-14); (iii) cyclosporine (25 mg/kg, i.p., daily, days 0-14), (iv) blocking monoclonal antibodies (mAbs) to CD4 and CD8 (2 mg, i.p., starting day 0 and on alternating days thereafter for a total of six doses), (v) tacrolimus plus mAbs, and (vi) cyclosporine plus mAbs. RESULTS: Allograft survival was prolonged in both the tacrolimus and cyclosporine groups. mAbs alone induced tolerance, and mAbs combined with tacrolimus also induced tolerance. In contrast, the combination of mAbs and cyclosporine was toxic. CONCLUSIONS: The induction of tolerance by blocking CD4 and CD8 was not prevented by tacrolimus. However, combination of cyclosporine with the same tolerogenic protocol was toxic to mice.

Animals↗

PubMed2003

Effect of dose of hypertonic saline on its potential to prevent lung tissue damage in a mouse model of hemorrhagic shock.

Recent studies have shown that hypertonic saline (HS) resuscitation can reduce hemorrhage-induced lung damage by preventing neutrophil activation. In this study, we examined whether this protective effect can be improved by increasing the HS dose used for resuscitation. The protective effect of two HS doses was tested in a mouse model of hemorrhagic shock. BALB/c mice were bled to a mean arterial blood pressure of 35 +/- 5 mmHg for 1 h. Then the animals were resuscitated with lactated Ringer's (LR) or with HS (7.5% NaCl) at doses of 4 mL/kg or 6 mL/kg body weight, sacrificed after 24 h, and lung tissue samples were collected. Evidence of lung injury was evaluated morphologically by scoring histology specimens in a blinded fashion. In a separate set of mice, plasma Na+ and osmolarity were determined 15 min after resuscitation. Resuscitation of hemorrhaged mice with 4 and 6 mL/kg HS increased plasma Na+ concentrations by 5 and 11 mM, respectively. LR treatment reduced plasma Na+ concentrations by 6 mM and resulted in a lung injury score of 6.1 +/- 0.8, accompanied by focal thickening of alveolar membranes, congestion, pulmonary edema, and interstitial and intra-alveolar neutrophil infiltration. HS at 4 mL/kg decreased focal thickening, congestion, pulmonary edema, and neutrophil infiltration, and the injury score to 3.8 +/- 0.9, which was not significantly different from controls (3.6 +/- 0.8), and lung damage was lowest in animals that received 6 mL/kg HS (2.5 +/- 0.2, P < 0.005 vs. LR). Lung damage scores inversely correlated with plasma Na+ concentrations (r > 0.9999). Our data suggest that the protective effect of HS may be a function of the plasma Na+ concentration and that HS at 6 mL/kg is at least equally effective in reducing hemorrhage-induced lung damage compared to the more commonly used HS dose of 4 mL/kg.

Animals↗

PubMed2000

Th1-Th2 cytokine kinetics in the bronchoalveolar lavage fluid of mice infected with Cryptococcus neoformans of different virulences.

Th1 immune response plays an important role in protection against infection with Cryptococcus neoformans in mice. We investigated the effect of virulence of C. neoformans on cytokine production in the lung of a mouse model of pulmonary cryptococcosis. BALB/c mice were inoculated intratracheally with a high or low virulence strain of C. neoformans, followed by serial measurements of Th1 and Th2 cytokine concentrations in the bronchoalveolar lavage (BAL) fluid using appropriate enzyme-linked immunosorbent assay kits. The number of colony-forming units (CFU) increased with time, and all mice infected with the highly virulent strain were dead at 28 days after inoculation. In contrast, the number of microorganisms diminished with time in the mice infected with the low virulence strain during the 4-week study. The numbers of neutrophils and lymphocytes in the BAL fluid paralleled those of CFU. High neutrophil counts were observed in the BAL fluid of mice infected with the highly virulent strain, while lymphocyte counts were increased only in the later part of the study in mice infected with the high and low virulence strains. The concentrations of Th2 cytokine, interleukin (IL)-4 were significantly higher in mice infected with the highly virulent strain at days 14 and 21 of infection, whereas the level of Th1 cytokine, interferon-gamma, was significantly higher in the latter strain at days 7 and 14. Our results suggest that strain-specific difference in the organism's ability to induce (or evade) the host immune system contributes to the outcome of infection.

Animals↗