Abstract:
:Elevation of intracellular cAMP levels has been shown previously to inhibit cytokine secretion by various cell types in vitro. Since salmeterol is a beta 2-agonist which activates adenylate cyclase, its ability to inhibit cytokine production was evaluated. Though salmeterol, and the related drug albuterol, did not inhibit IL-1 beta production in vitro, both drugs did inhibit tumour necrosis factor-alpha (TNF-alpha) secretion by lipopolysaccharide (LPS)-activated THP-1 cells with similar IC50s of approximately 0.1 microM. This inhibition was effectively reversed by the beta 2-antagonist oxprenolol, indicating that the inhibition was mediated through the beta 2-adrenergic receptor. A strikingly different reactivity profile was seen with T cells. Salmeterol was able to inhibit the activation of both mouse and human T cells, as measured by proliferation and IL-2 secretion in response to anti-CD3 antibody, whereas albuterol was completely inactive in these assays. This T cell inhibition by salmeterol was about 10-fold less potent than that for TNF-alpha production, and was not reversed by a beta 2-antagonist, indicating that a different mechanism was involved in the effect of salmeterol on T cells. Paralleling the TNF-alpha inhibitory activity in vitro, oral dosing of salmeterol and albuterol inhibited LPS-induced increase in murine serum TNF level in vivo, with ED50s of approximately 0.1 mg/kg. This inhibition could be abrogated by dosing orally with the beta-blocker propranolol. The long-acting pharmacological profile of salmeterol was apparent in that it maintained its efficacy for 3 h, while albuterol had a much shorter duration of action. Salmeterol also had some protective effects in the galactosamine/LPS model of endotoxic shock, which is dependent upon TNF-alpha production. Though salmeterol inhibited serum TNF-alpha levels by up to 94% in this assay, it protected less than 50% of the animals from the lethal effects of the LPS/galactosamine mixture. This observation suggests that functional levels of TNF-alpha localized in tissues may not be accurately reflected by serum levels.
journal_name
Clin Exp Immunoljournal_title
Clinical and experimental immunologyauthors
Sekut L,Champion BR,Page K,Menius JA Jr,Connolly KMdoi
10.1111/j.1365-2249.1995.tb05573.xsubject
Has Abstractpub_date
1995-03-01 00:00:00pages
461-6issue
3eissn
0009-9104issn
1365-2249journal_volume
99pub_type
杂志文章abstract::Significant numbers of syncytial cells were observed in the bronchoalveolar lavage fluid (BALF) of a 42-year-old patient who had SLE with interstitial pneumonia. Electron microscopic study of the BALF cells and positive reverse transcriptase activity in the supernatant of the cultured cells revealed unknown retroviral...
journal_title:Clinical and experimental immunology
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abstract::Immunoglobulin G (IgG) in soluble and particulate fractions of discrete tissue samples from multiple sclerosis (MS) brain was analysed. Supernatant IgG/albumin rations and particulate-bound IgG levels were highest in samples dissected from MS plaques and adjacent white matter. Acid extracts of particulate fractions fr...
journal_title:Clinical and experimental immunology
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journal_title:Clinical and experimental immunology
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journal_title:Clinical and experimental immunology
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journal_title:Clinical and experimental immunology
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abstract::Human IgD myeloma proteins are shown to have a high carbohydrate content (9-18%) and to exhibit the same heterogeneity in carbohydrate content and composition as myeloma protein of the other immunoglobulin classes. All IgD proteins studied contain N-acetylgalactosamine which is contained in a carbohydrate moiety attac...
journal_title:Clinical and experimental immunology
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更新日期:1975-11-01 00:00:00
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journal_title:Clinical and experimental immunology
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pub_type: 杂志文章
doi:10.1111/j.1365-2249.1994.tb06110.x
更新日期:1994-09-01 00:00:00
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journal_title:Clinical and experimental immunology
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doi:
更新日期:1978-04-01 00:00:00
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journal_title:Clinical and experimental immunology
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doi:10.1111/j.1365-2249.1995.tb05543.x
更新日期:1995-02-01 00:00:00
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pub_type: 杂志文章,评审
doi:10.1111/cei.12836
更新日期:2017-01-01 00:00:00
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journal_title:Clinical and experimental immunology
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doi:
更新日期:1987-05-01 00:00:00
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journal_title:Clinical and experimental immunology
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doi:
更新日期:1981-02-01 00:00:00
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journal_title:Clinical and experimental immunology
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abstract::Bone marrow transplantation (BMT) recipients are immunosuppressed and are at risk for contracting severe infections. Recently, adoptive transfer of immunity against hepatitis B virus (HBV) was documented in BMT recipients receiving bone marrow from 'naturally' HBV-infected individuals who recovered spontaneously, or t...
journal_title:Clinical and experimental immunology
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doi:10.1111/j.1365-2249.1994.tb06084.x
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journal_title:Clinical and experimental immunology
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
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更新日期:1992-06-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
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更新日期:1979-09-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1985-03-01 00:00:00
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journal_title:Clinical and experimental immunology
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::Serum factors activating the alternative pathway of complement in vitro, independent of classical pathway activation was demonstrated in six of eleven patients with systemic lupus erythematosus (SLE). These serum factors were detected by lysis of gluthathione-sensitized human erythrocytes and by C3 and factor B conver...
journal_title:Clinical and experimental immunology
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更新日期:1976-10-01 00:00:00