Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:BIOD00035 (CSF)
 30,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In spite of a history of more than 100 years, the pathoaetiology of multiple sclerosis is still unknown today. Research is based on three working hypotheses, i.e. on an immunopathological disease origin, on the conception that MS, as an infectious disease, is caused by a specific pathogen (slow virus infection) and on the assumption of a disturbance of basal metabolism or utilisation. The present position of the scientific foundation of the working hypotheses is presented in detail and supplemented by the results of our own investigations. Of particular interest are the geomedical studies which show that MS occurs more frequently in temperate climatic regions. In Europe, a latitude of 46 degrees forms a conspicuous boundary; in the USA this boundary is found at 38 degrees. North of this line there is a morbidity rate of 30 to 60 patients per 100 000 inhabitants, while south of it 15 cases at most per 100 000 inhibitants are found. Asia, especially in China and Japan, and tropical countries, where Multiple Sclerosis is practically unknown in the native populations, are exceptions. The observation that immigrants from areas with a low MS incidence into regions with a high risk of MS fall ill with the disease after years remains also unexplained. These peculiarities have given rise to the consideration whether there is a still unknown factor in the soil of high-risk areas or a specific pathogenic spectrum. In this connection, the question is also discussed whether the risk of MS in northern countries is associated with the excessive consumption of animal fat. The possible therapeutic and prophylactic significance of unsaturated fatty acids is emphasized. Our own results with the Schilling-test, determination of gastric acids, rubella titres in serum and cerebrospinal fluid, the immunofluorescence test of the serum and CSF, determination of tissue antigens (HLA) in families with multiple incidence of Multiple Sclerosis are discussed. On evaluation of a large series of patients, it is striking that Multiple Sclerosis and juvenile diabetes seem to be mutually exclusive (Schrader). Likewise, in MS statistics no other immunopathologic disease such as rheumatic diseases or bronchial asthma was found. Interestingly, also in 400 MS patients examined, hyperuricaemia or gout, which are widespread among the populace, were not found in a single case.
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PMID:[Pathogenesis of multiple sclerosis. Work-hypotheses and experimental data]. 84 79

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

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

In human beings, as in mice, two distinct patterns of cytokine secretion have been defined among CD4+ helper T-cell clones. Human type 1 helper (Th1), but not type 2 helper (Th2), cells produce interleukin-2 (IL-2), gamma-interferon (IFN-gamma), and tumor necrosis factor-beta, whereas Th2, but not Th1, cells secrete IL-4 and IL-5, but not IL-2 or IFN-gamma. Other cytokines, such as IL-3, IL-6, GM-CSF, or TNF-alpha, are produced by both Th1 and Th2 cells. Th0 cells, a third Th subset, show combined production of Th1- and Th2-type cytokines. The different cytokine patterns are associated with different functions. In general, Th2 cells provide an excellent helper function for B-cell antibody production, particularly of the IgE class. On the other hand, Th1 cells are responsible for delayed type hypersensitivity reactions and are cytolytic for autologous antigen-presenting cells, including B cells. Most allergen- or helminth-antigen-specific human CD4+ T-cell clones exhibit a Th2 phenotype, whereas most clones specific for bacterial antigens show a Th1 profile. Allergen-specific Th2 cells seem to play a crucial role in atopy. These cells induce IgE production via IL-4 and favor the proliferation, differentiation, and activation of eosinophils via IL-5. In addition, Th2-derived IL-3 and IL-4 are mast-cell growth factors that act in synergy, at least in vitro. Recent evidence indicates that allergen-specific Th2 cells are selectively enriched in tissues affected by allergic inflammation, such as the bronchial mucosa of subjects with allergic asthma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human Th1 and Th2 lymphocytes: their role in the pathophysiology of atopy. 148 46

Early studies of patients dying from status asthmaticus revealed marked inflammation of the bronchial tree. Subsequent histological studies of the airways and examination of bronchoalveolar lavage fluid of subjects with mild asthma have confirmed the presence of airway inflammation in life. There is epithelial edema and desquamation, subepithelial deposition of collagen and fibronectin, and an inflammatory cell infiltrate in the mucosa. There are increased numbers of activated eosinophils, CD25-positive T lymphocytes, and immature macrophages with the phenotypic characteristics of blood monocytes. An increased expression of HLA class II is present on epithelium, macrophages, and other infiltrating cells. The severity of clinical asthma correlates with several measurements of the severity of the inflammatory response, suggesting a crucial role for airway inflammation in the pathophysiology of the disease. There is considerable interest and research into the mechanisms underlying the pathogenesis and maintenance of the inflammatory response in asthma. The development and maintenance of the inflammatory response in asthma is likely to be a consequence of a complicated interaction between various cells and the mediators they generate. The characterization of an ever-increasing number of cytokines is of particular interest. Interleukin-3, interleukin-5, and granulocyte-macrophage colony-stimulating factor are hematopoietic growth factors that increase the survival of eosinophils in culture and enhance certain eosinophil functions, such as mediator generation and toxicity. Alveolar macrophages derived from asthmatic subjects produce twofold to threefold more GM-CSF than do those from normal control subjects. Using in situ hybridization, the presence of IL-5 mRNA has been demonstrated in bronchial biopsies from asthmatic subjects. Thus IL-3, IL-5, and GM-CSF influence eosinophil function and survival, and may be generated by T lymphocytes and/or alveolar macrophages within the airways in asthma. In addition to these three cytokines, IL-4 and interferon-gamma may be crucial to the regulation of IgE biosynthesis. TNF-alpha and IL-1 are potentially important in the up-regulation of endothelial adhesion molecules. An important step in the recruitment of leukocytes to an inflammatory focus is margination to the vascular endothelium. Our understanding of the molecular events involved in migration of leukocytes to an inflammatory focus has been advanced by the discovery and characterization of a variety of cell adhesion molecules. The potential role of ELAM-1 and ICAM-1 in allergic inflammation is suggested by their up-regulation on vascular endothelium in association with late cutaneous responses to allergen and by their role in certain primate models of asthma.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The pathobiology of bronchial asthma. 150 77

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

Lymphokines derived from activated T cells regulate the proliferation and postmitotic differentiation of eosinophils in vitro. We investigated whether peripheral blood eosinophilia, which is a characteristic feature of both allergic and nonallergic asthma, correlates with T cell activation and lymphokine production in asthmatic patients. Flow cytometric analysis of T cell activation markers revealed that asthmatic individuals are characterized by increased numbers of IL-2R (CD25)-bearing T cell subsets. The absolute number of IL-2R+ T cells correlated with the eosinophilia observed in the asthmatic patients. Purified CD4+ and CD8+ T cells from allergic and nonallergic asthmatic individuals spontaneously secreted factors that extend the lifespan of eosinophils in vitro. T cells from normal donors displayed this effect only after polyclonal stimulation with anti-CD3 antibody. The eosinophil lifespan-extending factors were also found in sera of asthmatic patients. Identification of these factors was performed by using neutralizing antibodies against IL-3, IL-5, and granulocyte-macrophage CSF. In sera, mainly IL-5 and granulocyte-macrophage CSF were responsible for prolonged eosinophil survival, whereas granulocyte-macrophage CSF was dominant in T cell supernatants. These results indicate that T cells and secretion of lymphokines play an important regulatory function toward eosinophils, which are thought to represent major proinflammatory effector cells in certain types of asthma.
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PMID:T cell subsets and their soluble products regulate eosinophilia in allergic and nonallergic asthma. 167 34

We report a 43-year-old male with hypereosinophilic syndrome. The patient has had eosinophilia since the age of 25. He developed bronchial asthma at 41 years of age. In the following year, he consulted a gastroenterologist because of fever and abdominal discomfort. Upper gastrointestinal study showed duodenitis. At the age of 43 years, there was slight fever, watery diarrhea, and eosinophilia. Examination in our department disclosed hypereosinophilic syndrome associated with duodenitis, endomyocarditis with an intraventricular thrombus, and bronchial asthma caused by house dust. Both prednisolone and aspirin were administered with improvement of eosinophilia and partial thrombolysis. Assays of IL-3, GM-CSF, and IL-5 revealed increased activity of IL-5, GM-CSF, and IL-3 in this order. Especially IL-5 has by far the strongest activity in these cytokines. IL-5 may play an important role in the development of hypereosinophilic syndrome.
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PMID:[A case of hypereosinophilic syndrome followed by bronchial asthma, intraventricular thrombus, and duodenitis]. 175 11

Cultured human bronchial epithelial cells constitutively produce granulocyte/macrophage colony-stimulating factor (GM-CSF). An upregulation of the synthesis and release of GM-CSF from those cells might contribute to the persistence of infiltration and local activation of inflammatory cells in some inflammatory diseases of the airways, such as asthma. Increased levels of immunoreactive and biologically active interleukin-1 (IL-1) have been identified in the airway secretions of asthmatic patients, together with an increase in GM-CSF contents. As IL-1 is known to upregulate GM-CSF production in many cell populations, in this study we investigated the ability of IL-1 to bind to specific receptors on bronchial epithelial cells and promote GM-CSF synthesis and release. Bronchial epithelial cells possessed specific single-class surface receptors for recombinant IL-1. The addition of exogenous IL-1 led to a dose-dependent increase in the accumulation of GM-CSF mRNA and release of immunoreactive GM-CSF to the culture medium. Release of IL-1 in the bronchial mucosa during allergic and nonallergic responses may lead to enhanced GM-CSF synthesis and release by epithelial cells, thus promoting airway inflammation.
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PMID:Interleukin-1 binds to specific receptors on human bronchial epithelial cells and upregulates granulocyte/macrophage colony-stimulating factor synthesis and release. 182 52


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