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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the immune responses to intestinal nematode infection have been well studied and have been shown to be strongly driven by Th2-associated cytokines in mice, such information has been limited with respect to rats. We investigated changes in levels of the mRNAs encoding interleukin-2 (IL-2), IL-3, IL-4, IL-5, IL-10, and gamma interferon in the mesenteric lymph nodes of rats infected with Nippostrongylus brasiliensis by reverse transcription-PCR in comparison with immunoglobulin E (IgE)/IgG2a antibody, eosinophil, basophil, and mucosal mast cell responses. In the two rat strains used, Brown Norway and Fischer-344, which show different responses to allergens, serum IgE increased to much higher levels in the former than in the latter 2 weeks after infection. Intestinal mastocytosis was observed much earlier and more intensely in Brown Norway rats than in Fischer-344 rats, but the degrees of peripheral eosinophilia and basophilia did not differ between the two strains. In both strains, IL-3, IL-4, and IL-5 mRNA expression increased and peaked around 7 to 14 days after infection, while expression of IL-2, IL-10, and gamma interferon mRNAs did not change notably throughout the experimental period. The highest IL-4 mRNA expression was observed slightly earlier in Brown Norway than in Fischer-344 rats, but levels of IL-3 and IL-5 mRNAs peaked synchronously in both strains. The amounts of mRNAs encoding these three cytokines were always higher in Brown Norway than in Fischer-344 rats. It is suggested that in rats, Th2 or Th2-like cells are also induced after nematode infection, and IgE elevation is mainly related to increased IL-4 gene expression.
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PMID:Cytokine mRNA expression profiles in rats infected with the intestinal nematode Nippostrongylus brasiliensis. 759 Nov 19

We determined the expression of Th-2 type cytokines, interleukin-4 (IL-4) and IL-5, and of the Th-1 type cytokine, interferon-gamma (IFN-gamma), in the Brown-Norway rat. Rats were intraperitoneally sensitized with ovalbumin and 21 days later were either exposed to ovalbumin or saline aerosol. The value -log PC300 (PC300 = concentration of acetylcholine needed to increase baseline lung resistance by 300%) was 2.49 +/- 0.15 in sensitized, exposed rats, was higher than in sensitized, saline-exposed or naive rats (1.54 +/- 0.27 and 1.63 +/- 0.06 respectively, P < 0.05). There was a significant increase in eosinophils in bronchoalveolar lavage fluid and in airway submucosal airway tissues in the sensitized exposed group. Reverse-transcriptase polymerase chain reaction was performed on total lung RNA using primers for IL-4, IL-5, IFN-gamma and beta-actin. IL-4 and IL-5 mRNA levels in control and sensitized saline-exposed rats were not detectable, but increased levels were found in sensitized and ovalbumin-exposed rats with levels of 0.25 +/- 0.01 and 0.98 +/- 0.02% of beta-actin mRNA as assessed by densitometric measurements. Expression of IFN-gamma mRNA was significantly reduced in sensitized and ovalbumin-exposed rats. As in asthmatic airways, there is an increased expression of Th-2 cytokines, IL-4 and IL-5, together with a reduction in the Th-1 cytokine, IFN-gamma, thus supporting a role for Th-2 cytokines in allergic eosinophilic inflammation.
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PMID:Expression of Th-2 cytokines interleukin-4 and -5 and of Th-1 cytokine interferon-gamma in ovalbumin-exposed sensitized Brown-Norway rats. 869 Apr 57

To assess whether Th-2 cytokines are involved in the late airway response (LR) after antigen challenge, we evaluated cytokine mRNA expression in the lungs of two strains of rats before and 8 h after saline or antigen challenge: Brown Norway (BN) rats, high IgE producers that develop LR after antigen challenge and Sprague-Dawley (SD) rats, low IgE producers that develop little LR and no increased airway responsiveness after antigen challenge. Rats were sensitized with ovalbumin (OA) and 14 days later, lungs were obtained before or after OA challenge and measurement of lung physiology for 8 h. Lung tissue was either fixed for in situ hybridization or frozen for evaluation of mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). We examined mRNA expression for interleukin-4 (IL-4), and IL-5 (Th-2 cytokines) and IL-2 and interferon gamma (IFN-gamma, Th-1 cytokines). In situ hybridization showed that cells expressing IL-4 and -5 mRNA were increased in the airways of the lungs of BN rats after OA challenge (P < 0.05) and that cells expressing mRNA for IFN-gamma and IL-2 were higher in SD than in BN rats after antigen challenge (P < 0.05). Results from PCR showed that prior to antigen challenge, BN rats expressed in their lungs mRNA for IL-4 and -5 and SD rats expressed very little mRNA for IL-5 only. After antigen challenge most BN and SD rats expressed mRNA for IL-4 and -5 but expression of mRNA for IL-2 and IFN-gamma was only found in SD rats. In conclusion, rats that develop a LR after antigen challenge preferentially increase Th-2 cytokine expression in their lungs whereas those without LRs preferentially express Th-1 cytokines. Our results support the role of Th-2 cytokines in the LR and asthma.
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PMID:Cytokine expression in the presence or absence of late airway responses after antigen challenge of sensitized rats. 881 Jun 41

Mercuric chloride (HgCl2) has contrasting effects on different rat strains: susceptible strains, e.g. Brown Norway (BN) develop polyclonal B cell activation, multiple autoantibodies and widespread tissue injury. Lewis (LEW) rats are resistant: no autoimmune response occurs after HgCl2; instead, there is immunosuppression. We have previously shown, by fully quantitative polymerase chain reaction (PCR), up-regulation of interleukin-4 (IL-4) gene expression in HgCl2-treated BN rats, implicating Th2 cells in the autoimmune syndrome. Involvement of the reciprocal Th1 subset, producing interferon-gamma (IFN-gamma), in resistance of LEW rats to HgCl2 has been suggested. We now report extensive analysis of Th1 and Th2 cytokine gene expression in spleen and lymph nodes of susceptible (BN) and resistant (LEW) rats after HgCl2. IL-4 and IFN-gamma were analyzed by quantitative PCR, other cytokines were assessed using semiquantitative PCR: the relative merits of these two techniques are discussed. We show pronounced up-regulation of IL-4 and more modest up-regulation of IFN-gamma in BN rats, but no up-regulation of either in LEW rats. Baseline levels of IFN-gamma were higher in Lew rats. Semiquantitative PCR showed increased expression of IL-2, IL-6 and IL-10 in BN; in LEW rats only IL-10 was increased. There was no marked change in IL-5, IL-13 or transforming growth factor-beta (TGF-beta) in either strain. These data further support the key role of IL-4 in HgCl2-induced autoimmunity, and suggest that failure of up-regulation of IL-4, together with higher baseline IFN-gamma expression, accounts for resistance of LEW rats to HgCl2. However, neither IFN-gamma nor TGF-beta can be implicated in HgCl2-induced immunosuppression in the LEW rat in vivo: our data suggest a role for IL-10 in this phenomenon.
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PMID:Th1/Th2 cytokine gene expression after mercuric chloride in susceptible and resistant rat strains. 889 50

Current evidence suggests that the events subsequent to antigen challenge in allergic asthmatics involve eosinophil activation and the synthesis of proinflammatory cytokines, in particular interleukin 5 (IL-5). However, little is known about how local inflammatory cell infiltration and activation are related to the changes in lung function following allergen exposure. We have developed a novel technique to investigate the local inflammatory events during late-onset allergic bronchoconstriction in lung explants from sensitized Brown-Norway (BN) rats. In this study we tested the hypothesis that the in vitro late airway response involves IL-5 gene activation and recruitment and activation of eosinophils. Explants were prepared from excised lungs of BN rats (n = 9) sensitized 2 wk previously to ovalbumin (OVA). Lungs were inflated with liquid agarose solution (2% wt/vol, 48 ml/kg) following perfusion with cold Ca2+/Mg(2+)-free Hanks' solution, and refrigerated briefly to gel the agarose, and 0.5- to 1.0-mm slices were prepared and cultured overnight at 37 degrees C. Airways were identified and challenged by direct application of OVA (20 micrograms). Cryostat sections of explants were immunostained for major basic protein (MBP) and IL-5 mRNA was detected by a 35S-uridine triphosphate-labeled probe and in situ hybridization. Explants harvested immediately prior to challenge showed little evidence of MBP and IL-5 mRNA expression. Explants harvested at 6 h which exhibited evidence of bronchoconstriction showed strong cell-associated immunostaining for MBP and high expression of IL-5 mRNA in the bronchial mucosa. colocalization studies performed in lung explants demonstrating late-onset airway responses suggested that the majority of IL-5 mRNA expression was not found in MBP-positive cells. When compared with explants from sham-sensitized rats (n = 4), there was a significant increase in MBP-positive and IL-5 mRNA-positive cells per millimeter of basement membrane of the airway. The presence of MBP immunoreactivity and IL-5 gene expression was not observed in explants taken from sensitized BN rats which did not undergo late-onset airway responses, indicating an association between inflammatory cell activation and airway constriction. The increase in MBP-positive cells several hours after OVA suggests activation, local recruitment, and/or differentiation of eosinophils. This study provides direct evidence for a temporal association between IL-5 expression, eosinophil infiltration, and the late response in individual cultured airways.
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PMID:Evidence for major basic protein immunoreactivity and interleukin 5 gene activation during the late phase response in explanted airways. 891 65

Sensitizing chemicals can induce various types of allergic disease, including contact dermatitis and occupational asthma. In the present study we have examined the nature of the immune response induced in Brown Norway (BN) rats by oxazolone (OX), a potent contact allergen, and by trimellitic anhydride (TMA), a chemical known to cause sensitization of the respiratory tract and occupational asthma. BN rats were exposed topically to either OX or TMA at doses selected to achieve similar levels of proliferative activity by draining LNC. Both chemicals stimulated hapten-specific IgG antibody responses, but only TMA induced specific IgE antibody, an increase in total serum IgE and active sensitization of mast cells. Draining LNC from OX-treated rats expressed elevated IFN-gamma mRNA, whereas those from TMA-treated rats expressed elevated IL-5 mRNA compared to controls. Furthermore, Con A-activated draining LNC from rats exposed to TMA, but not OX, released significantly increased concentrations of IL-4. In conclusion, different chemical allergens can induce in the BN rat divergent patterns of IgE response and cytokine expression.
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PMID:Selectivity of IgE responses, mast cell sensitization, and cytokine expression in the immune response of Brown Norway rats to chemical allergens. 896 87

Late allergic airway responses can be transferred by CD4+ T cells in the rat. To investigate the role of T-cell cytokines in these responses, we examined the expression of mRNA for Th2 (interleukin [IL]-4 and IL-5) and Th1 (IL-2 and interferon gamma [INF-gamma])-type cytokines in Brown Norway rats that were administered either antigen-primed W3/25(CD4)+ or OX8(CD8)+ T cells. Donors were actively sensitized by subcutaneous injection of ovalbumin (OVA) in the neck and T cells were obtained from the cervical lymph nodes by immunomagnetic cell sorting for administration to unsensitized rats. Control rats received bovine serum albumin (BSA)-primed CD4+ and CD8+ T cells. Two days later, recipient rats were challenged with aerosolized OVA, and bronchoalveolar lavage (BAL) was performed 8 h after challenge. BAL cells expressing mRNA for IL-2, IL-4, IL-5, and INF-gamma were analyzed using the technique of in situ hybridization. Recipients of OVA-primed CD4+ T cells had an increase in the fraction of BAL cells expressing mRNA for IL-4 and IL-5 compared with BSA-primed CD4+ or OVA-primed CD8+ cells (P < 0.001). Recipients of CD8+ T cells had an increase in INF-gamma mRNA expression after OVA challenge compared with recipients of BSA-primed-CD8+ or OVA-primed CD4+ T cells (P < 0.001). In conclusion, T-cell-dependent allergen-induced late responses are associated with the expression of mRNA for IL-4 and IL-5, indicating Th2 cell activation. Furthermore, the increased expression of INF-gamma in allergen challenge recipients of antigen-primed CD8+ T cells suggests that CD8+ T cells may be important in modulating allergic responses.
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PMID:Adoptively transferred late allergic airway responses are associated with Th2-type cytokines in the rat. 899 81

To investigate the effect of aging on the allergic airway response, we examined the bronchoconstrictive responses and cellular inflammatory changes in a rat model of bronchial asthma by evaluating young and old animals. Two different age groups of Brown-Norway rats, actively sensitized by injection of ovalbumin into the foot pads, were used: 7 to 8 weeks old (young group) and 100 to 120 weeks old (aged group). Both the aged and young rats produced on ovalbumin-specific IgE antibody and exhibited an immediate asthmatic response after exposure to ovalbumin, but the degree of specific IgE antibody was significantly higher in young rats. The young group showed a marked increase in the number of eosinophils and neutrophils in bronchoalveolar lavage fluid 2 days after exposure to ovalbumin, whereas no eosinophilia was seen in the aged group. To evaluate the mechanism of the decreased accumulation of eosinophils in aged rats, cells from popliteal lymph nodes from ovalbumin-sensitized rats were incubated with ovalbumin for 48 hours. Although eosinophil chemotactic activity, determined by a modified Boyden chamber method, was present in the supernatant of cultured lymph node cells from young rats, it was absent from those of aged rats. In vivo administration of anti-IL-5 monoclonal antibody revealed that one of the factors of eosinophil chemotactic activity was IL-5. Lymph node cells from aged rats tended to produce greater amounts of interferon-gamma than did those from young animals. Findings indicate that aged rats have a defect in eosinophil accumulation in sites exposed to antigen, probably because of an age-dependent alteration in T cells.
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PMID:Failure of aged rats to accumulate eosinophils in allergic inflammation of the airway. 900 9

1. The effects of a novel 17-thiosteroid, RPR 106541, were investigated in a rat model of allergic airway inflammation. 2. In sensitized Brown Norway rats, challenge with inhaled antigen (ovalbumin) caused an influx of eosinophils and neutrophils into the lung tissue and airway lumen. In the lung tissue there was also an accumulation of CD4+ T lymphocytes and increased expression of mRNA for interleukin-4 (IL-4) and IL-5, but not interferon-gamma (IFN-gamma). These findings are consistent with an eosinophilia orchestrated by activated Th2-type cells. 3. RPR 106541 (10-300 microg kg[-1]), administered by intratracheal instillation into the airways 24 h and 1 h before antigen challenge, dose-dependently inhibited cell influx into the airway lumen. RPR 106541 (100 microg kg[-1]) caused a significant (P<0.01) (98%) inhibition of eosinophil influx and a significant (P<0.01) (100%) inhibition of neutrophil influx. RPR 106541 was approximately 7 times and 4 times more potent than budesonide and fluticasone propionate, respectively. 4. When tested at a single dose (300 microg kg[-1]), RPR 106541 and fluticasone each caused a significant (P<0.01) (100%) inhibition of CD4+ T cell accumulation in lung tissue. Budesonide (300 microg kg[-1]) had no significant effect. RPR 106541 and fluticasone (300 microg kg[-1]), but not budesonide (300 microg kg[-1]), significantly (P<0.05) inhibited the expression within lung tissue of mRNA for IL-4. RPR 106541 (300 microg kg[-1]) also significantly (P<0.05) inhibited expression of mRNA for IL-5. 5. The high topical potency of RPR 106541 in this model, which mimics important aspects of airway inflammation in human allergic asthmatics, suggests that this glucocorticoid may be useful in the treatment of bronchial asthma.
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PMID:RPR 106541, a novel, airways-selective glucocorticoid: effects against antigen-induced CD4+ T lymphocyte accumulation and cytokine gene expression in the Brown Norway rat lung. 935 99

The production of immunoglobulin E (IgE) antibody is largely dependent on the ratio between interleukin-4 (IL-4) (a T helper 2 (Th2)-type cytokine) and interferon-gamma (IFN-gamma) (a T helper 1 (Th1)-type cytokine). Interleukin-5 (IL-5) (also a Th2-type cytokine) is an important eosinophil differentiation factor and also co-stimulates B-cell growth and differentiation. The present study was designed to evaluate and compare the expression of IFN-gamma, IL-4 and IL-5 mRNA in the nasal mucosal membrane of sensitized Brown-Norway (BN) rats. Fourteen BN rats were divided into two groups: non-sensitized (control) and sensitized. The sensitized group was injected with ovalbumin (OA) intraperitoneally on three consecutive days. Twenty-one days later, rats were exposed to 1% OA aerosol. Twenty-four hours after exposure to aerosol, nasal mucosa was extracted from both groups and reverse transcriptase-polymerase chain reaction (RT-PCR) was performed. The densities of the bands of IL-4, IL-5 and IFN-gamma mRNA were expressed as percentages against beta-actin mRNA. Our results showed that the mean values for IL-4 and IL-5 mRNA were increased significantly in sensitized rats compared with control rats. In contrast, the mean value for IFN-gamma mRNA was significantly lower in sensitized rats compared with those of the control group. Our data therefore suggest that sensitization of rat nasal mucous membranes results in the predominant expression of Th2-type cytokines.
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PMID:Expression of interferon-gamma, interleukin-4 and interleukin-5 mRNA in the nasal mucosal membrane of rats with allergic rhinitis. 965 23


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