Isoproterenol regulates tumour necrosis factor, interleukin-10, interleukin-6 and nitric oxide production and protects against the development of vascular hyporeactivity in endotoxaemia

C. Szabó, G. Haskó, B. Zingarelli, Z. H. Németh, A. L. Salzman, V. Kvetan, S. Mccarthy Pastores, E. S. Vizi

    Research output: Contribution to journalArticle

    121 Scopus citations

    Abstract

    Pro-inflammatory cytokines, such as tumour necrosis factor (TNF) and free radicals, such as nitric oxide (NO), are mediators of endotoxaemia. Catecholamines are in clinical use to treat the haemodynamic consequences of severe septic shock. Beta-adrenergic agonists exert many of their effects by elevation of intracellular cyclic AMP (cAMP) concentration. Cyclic AMP can modulate endotoxin-induced cytokine and NO production. Here we investigate the effect of isoproterenol pretreatment on the cytokine and NO production induced by bacterial lipopolysaccharide (LPS, 4-10 mg/kg). Pretreatment with isoproterenol (10 mg/kg) blunted the LPS-induced TNF response, increased the LPS-induced formation of interleukin-10 and interleukin-6 and reduced the LPS-induced production of NO in conscious mice. In anaesthetized rats, pretreatment with isoproterenol prevented the LPS-induced suppression of vascular contractility to norepinephrine in the thoracic aorta ex vivo. The hyporeactivity is due to expression of the inducible isoform of NO synthase (iNOS) and was restored by in vitro administration of N(G)-methyl-L-arginine (L-NMA), an inhibitor of NO synthase. However, L-NMA did not alter vascular contractility in control vessels or in rings taken from the LPS-treated rats pretreated with isoproterenol. Our findings suggest that, in addition to its haemodynamic actions, isoproterenol may also exert beneficial effects by modulating the endotoxin-induced inflammatory response.

    Original languageEnglish (US)
    Pages (from-to)95-100
    Number of pages6
    JournalImmunology
    Volume90
    Issue number1
    DOIs
    StatePublished - 1997

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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