Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:BIOD00082 (IL-2)
 29,198 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously reported that the 5-day culture supernatants of peripheral blood mononuclear cells (PBMC) from Dermatophagides farinae (DF) sensitive asthmatics stimulated with 10 ng/ml DF antigen contain eosinophil chemotactic activity (ECA) with an apparent molecular weight greater than 30000 Da. In the present study, we examined the effects of CyA and FK on the ECA. ECA was tested using modified Boyden chamber method. We found that when CyA or FK was added to the culture throughout the experiment, the production of the factors with ECA by PBMC was inhibited in a dose-dependent manner. These inhibitory effects were unchanged by the addition of a sufficient dose of IL-2 to the culture medium. Isoelectrofocusing of the PBMC culture supernatants consistently yielded a major ECF activity at pH 7.0-7.5. The addition of CyA inhibited this major peak. In conclusion, these results suggest that mononuclear cells stimulated with related antigen produce substances which possess ECA and that CyA and FK can block the production of this substance. Therefore, there is a possibility that an immunosuppressive agent may be useful in bronchial asthma therapy by inhibiting the migration of eosinophils.
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PMID:[Inhibitory effects of cyclosporin A and FK-506 on eosinophil chemotactic factor activity in culture supernatants of mononuclear cells from asthmatics]. 128 86

The in vitro production of granulocyte/macrophage colony stimulating factor (GM-CSF) by mononuclear cells from the peripheral blood of patients with bronchial asthma (BA) was examined by enzyme-linked immunosorbent assay (ELISA). In 3 of 12 cases studied, mononuclear cells from BA patients produced GM-CSF without stimulation. And in 5 of 12 cases studied, mononuclear cells from BA patients produced GM-CSF in response to IL-2. Mononuclear cells from patients with other diseases (n = 13) and healthy volunteers (n = 6) did not release any detectable (> or = 7.5 pg/ml) GM-CSF. The culture media of mononuclear cells from BA patients showed activities for stimulating the proliferation and survival of eosinophils, and these activities were partially inhibited by anti-GM-CSF antibodies. GM-CSF production by mononuclear cells from BA patients treated with prednisolone was lower than that of mononuclear cells from untreated BA patients. And prednisolone showed a reduction in the GM-CSF production from mononuclear cells in response to IL-2. These results suggest that GM-CSF production by mononuclear cells may play a role in the pathogenesis of BA.
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PMID:[Increased granulocyte/macrophage colony stimulating factor production by mononuclear cells from patients with bronchial asthma]. 129 Apr 9

In asthma, a beta-adrenoceptor dysfunction may be the consequence of an active disease state rather than a fundamental abnormality. In the present study the possible involvement of T lymphocytes in beta-adrenergic impairment was investigated by studying the effects of lymphocyte-derived mediators of beta-adrenoceptor function of human peripheral blood mononuclear cells (PBMCs) and guinea pig trachea. Supernatants of phytohemagglutinin- or concanavalin A-activated PBMCs from either persons with asthma or healthy persons inhibited isoprenaline stimulated cyclic adenosine 3',5'-monophosphate (cAMP) production of PBMCs after 20 hours of preincubation. These supernatants also inhibited beta-adrenoceptor function of PBMCs from patients with asthma to the same extent. The isoprenaline stimulated cAMP production of PBMCs was not altered after a 2-hour preincubation period with human interleukin-1 (IL-1), IL-2, IL-3, IL-4, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon (IFN-gamma). In contrast, after 20 hours of preincubation, stimulated cAMP production of PBMCs was significantly diminished, with 63% by IL-1 (40 U/ml, p less than 0.01), with 36% by IL-2 (100 U/ml, p less than 0.05), with 37% by IFN-gamma (1000 U/ml, p less than 0.05), and with 21% by GM-CSF (100 U/ml, p less than 0.05). Preincubation of guinea pig tracheal segments with IL-1, IL-2, IL-4, or GM-CSF during 1 or 3 days did not affect the EC50 values or the maximal relaxation of isoprenaline dose response curves.
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PMID:Effects of cytokines on beta-adrenoceptor function of human peripheral blood mononuclear cells and guinea pig trachea. 132 72

To determine whether cytokines are generated in vivo in subjects with asthma, we have measured cytokine levels (tumor necrosis factor [TNF], granulocyte-macrophage-colony-stimulating factor [GM-CSF], interleukin [IL]-1 alpha, IL-1 beta, IL-2, IL-4, and IL-6) in the airways of subjects with symptomatic (N = 24) and asymptomatic (N = 9) asthma with immunoassays (GM-CSF, IL-1 alpha, IL-1 beta, IL-2, and IL-4) or bioassays (TNF and IL-6) and the polymerase chain reaction (IL-1 beta and TNF). Significant levels of TNF (578 +/- 917 pg/ml versus 24 +/- 29 pg/ml) (p = 0.01), GM-CSF (24 +/- 41 pg/ml versus less than 8 pg/ml) (p = 0.02), and IL-6 (225 +/- 327 pg/ml versus 7 +/- 12 pg/ml) (p = 0.01), but not IL-1 alpha or IL-4, were detected in the bronchoalveolar lavage fluid (BALF) of patients with symptomatic compared with BALF of patients with asymptomatic asthma. Levels of IL-1 beta (266 +/- 270 pg/ml versus less than 20 pg/ml) (p = 0.001) and IL-2 (1.4 +/- 2.8 ng/ml versus less than 0.3 ng/ml) (p = 0.05) in BALF in patients with symptomatic compared with that in BALF levels in patients with asymptomatic asthma suggested activation of alveolar macrophages and T cells. Thus, in episodes of asthma, several cytokines, including TNF, GM-CSF, IL-1 beta, IL-2, and IL-6 are detectable in BALF.
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PMID:Cytokines in symptomatic asthma airways. 137 72

Mononuclear phagocytic cells contain low affinity receptors for IgE (Fc epsilon RII or CD23) which induce cellular activation in the presence of specific allergen. These studies were performed to quantify the expression by monocytes and alveolar macrophages of Fc epsilon RII in asthma and to determine biologic response modifiers that regulate Fc epsilon RII. Whereas 2.5 +/- 1.0% of the monocytes obtained from normal volunteers were Fc epsilon RII positive, this increased to 16.7 +/- 2.4% in asthma (p < 0.001). Stimulation of Fc epsilon RII expression on monocytes was shown to be an activity of IL-4 (24.5 +/- 5.9%), granulocyte-macrophage-CSF (28.1 +/- 5.2%), IFN-alpha (15.8 +/- 5.3%), IFN-gamma (10.4 +/- 3.7%), and macrophage-CSF (7.3 +/- 0.7%) but not of IL-2, IL-6, or TNF-alpha. Expression of Fc epsilon RII by these cytokines was associated with the induction of specific mRNA transcripts. Using Fc epsilon RII subtype specific primers in the polymerase chain reaction expansion of cDNA, cytokine-induced receptors were shown to be Fc epsilon RIIb. Alveolar macrophages from nonasthmatic subjects displayed minimal expression of Fc epsilon RII (3.2 +/- 1.2%); however, these receptors were present on 69.2 +/- 6.3% of asthmatic volunteers (p < 0.001). Induction of Fc epsilon RII appears specific for allergic asthma insofar as these receptors are also not expressed in subjects with interstitial lung disease (1.3 +/- 1.3%). As assessed by shift in mean fluorescence, instillation of allergen in the asthmatic's airway further up-regulated Fc epsilon RII on alveolar macrophages by 151 +/- 7%. Up-regulation of Fc epsilon RII in atopic individuals may therefore reflect allergen-induced exposure of mononuclear phagocytes to one or more of these cytokines. These studies suggest a mechanism by which an immunologic stimulus that leads to the production of these cytokines (e.g., allergen or viral infection) would contribute to the development or exacerbation of allergic disease.
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PMID:Regulation of low affinity IgE receptor (CD23) expression on mononuclear phagocytes in normal and asthmatic subjects. 140 14

Late asthmatic response (LAR) as well as delayed asthmatic response (DeAR) is an important clinical characteristic in adult severe asthma. These responses might be based on cell to cell interaction following lymphocyte activation. Therefore, to clarify the pathogenesis of LAR, we studied the lymphocyte functions of adult asthmatics with LAR provoked by inhalation of house dust and Candida antigen. The results revealed that mite antigen-specific lymphocyte blastogenesis, IL-2 and ECF production were significantly higher in asthmatics with LAR provoked by house dust antigen than in normal subjects and asthmatics with IAR by house dust and LAR by Candida, though there was no significant difference in NCF. Candida antigen-specific lymphocyte blastogenesis, IL-2, ECF and NCF production were significantly higher in asthmatics with LAR provoked by Candida antigen than in normal subjects and asthmatics with IAR or LAR provoked by house dust. There was a positive correlation between Candida antigen-specific IL-2 and NCF production in asthmatics with LAR provoked by Candida antigen. These results suggest that antigen-specific lymphocyte activation may play an important role in the pathogenesis of LAR, especially in asthmatics with LAR provoked by Candida antigen, and that LAR and DeAR should be considered inclusively as cell-mediated allergy.
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PMID:[Studies of lymphocyte activation on late asthmatic response in adult asthma]. 144 26

The effect of glucocorticoids on interleukin-5 (IL-5) gene expression was assessed in human peripheral blood mononuclear cells. IL-5 expression was stimulated by phytohaemagglutinin (PHA), IL-2, phorbol myristate acetate (PMA) or Ionomycin. A semi-quantitative assay for IL-5 gene expression was developed, based on RNA extraction and the polymerase chain reaction. IL-5 expression in response to PHA was profoundly inhibited by 10(-6) M dexamethasone, and significant inhibition was detected at doses of dexamethasone as low as 10(-9) M. When dexamethasone was added to the cells at the same time as PHA, the inhibitory effect could be detected as early as 3 hr. Dexamethasone at 10(-6) M also profoundly inhibited the IL-5 response to PMA and to IL-2, but the IL-5 response to Ionomycin was not significantly affected. These results suggest that dexamethasone may be capable of interfering with a pathway involving protein kinase C. There is increasing evidence that IL-5 may play a pathogenic role in asthma and other manifestations of acute hypersensitivity. The present findings indicate that inhibition of IL-5 expression may be one of the mechanisms whereby glucocorticoids exert their beneficial effects in diseases such as asthma.
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PMID:Inhibition of interleukin-5 gene expression by dexamethasone. 149 21

We investigated peripheral blood B and T lymphocyte functions in atopic individuals. B cells were co-cultured with mutant EL4 thymoma cells in the presence of a standard T cell supernatant (T-SN) with or without exogenous interleukin (IL)-4. IgE secretion in this assay was found to be IL-4 dependent, but not significantly different for atopic patients (n = 25) vs. normal controls (n = 25). Phytohemagglutinin plus phorbol 12-myristate 13-acetate (PHA+PMA)- induced T-SN from patients or controls was tested on normal B cells in the same assay system (in the absence of exogenous IL-4). Compared to the controls, the IgE-inducing activity was significantly increased for patients with asthma or allergic rhinitis (n = 12; p less than 0.005) but not for patients with atopic dermatitis (n = 13). The difference between the asthma or allergic rhinitis vs. the atopic dermatitis groups was significant (p greater than 0.05). Since the assay was not inhibited by interferon (IFN)-gamma, this difference can not be attributed to IFN-gamma concentrations. Other T cell activities may be different between the patient groups or atopic T cells from the respiratory mucosa may recirculate more than those from the skin. In any case, the T cells rather than the B cells were found to be abnormal in atopic individuals. If atopic T cells were stimulated with PHA+PMA not as immediately but after a resting period of 48 h in culture medium alone, the IgE-inducing activity, but not the total Ig-inducing activity or the IL-2 secretion, disappeared. In addition, a mean of 37% of the IgE-inducing activity (range of 13% to 79% for five very active T-SN) was not inhibited by an anti-IL-4 antibody which neutralized exogenous IL-4, indicating a participation of factors capable of bypassing the requirement for IL-4 for the IgE response.
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PMID:T cells from atopic individuals produce IgE-inducing activity incompletely blocked by anti-interleukin-4 antibody. 154 25

To investigate the eosinophilia in patients with bronchial asthma (BA), we examined the release of eosinophil colony stimulating factor (Eo-CSF) from blood mononuclear cells (MNC) and lymphocytes from BA. We also investigated the effect of specific antigens on the release of Eo-CSF to determine its relation to other known Eo-CSFs. 1) Phytohaemagglutinin (PHA) and interleukin (IL)-2 at optimal concentrations stimulated mononuclear cells from BA, and induced Eo-CSF release. In contrast, MNC from normal volunteers released Eo-CSF with only PHA, but did not release Eo-CSF with IL-2. 2) Lymphocytes from BA who were sensitive to house dust mite and Dermatophagoides farinae (D. farinae) antigens responded to specific antigens with Eo-CSF production, but those from normal volunteers did not. 3) The anti-IL-3, anti-IL-5, and anti-granulocyte-macrophage (GM)-CSF antibody inhibited Eo-CSF activity in culture media of lymphocytes from BA. These results indicate that the increase in responsiveness of lymphocytes from BA to specific antigens and cytokines produced by T cells play an important role in the induction of eosinophilia in BA.
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PMID:[Eosinophil colony stimulating factor production by lymphocytes from patients with bronchial asthma]. 162 98

Activation of lymphocyte subpopulations was determined in conjunction with levels of cytokines in peripheral blood and bronchoalveolar lavage (BAL) of asthmatics. Allergic asthmatics had increased numbers of CD4+ IL-2R+ T cells in peripheral blood and BAL, and T-cell activation closely correlated with numbers of low-affinity IgE receptor (CD23) bearing B cells. In contrast, in nonallergic asthmatics both CD4+ and CD8+ T cells from blood and BAL had increased expression of IL-2R, HLA-DR, and VLA-1. Furthermore, in the nonallergic asthmatics CD8+ T cells were decreased in blood but increased in BAL. Cytokine levels were determined in BAL fluid and supernatants from purified peripheral blood T cells and enriched BAL lymphocyte preparations. Allergic asthmatics were characterized by increased levels of IL-4 and IL-5, and this elevated IL-4 contributed to the elevated IgE levels found in these allergic subjects. In contrast, nonallergic asthmatics had elevated levels of IL-2 and IL-5, with IL-2 contributing to T-cell activation. In both types of asthma, the close correlation of IL-5 levels with eosinophilia suggests that IL-5 is responsible for the characteristic eosinophilia of asthma. Thus, we provide evidence of distinct T-cell activation resulting in different spectra of cytokines in allergic and nonallergic asthma.
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PMID:Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. 162 92


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