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

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

Research output: Contribution to journalArticle

120 Citations (Scopus)

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
StatePublished - 1997
Externally publishedYes

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Endotoxemia
Isoproterenol
Interleukin-10
Blood Vessels
Interleukin-6
Nitric Oxide
Tumor Necrosis Factor-alpha
Cytokines
Endotoxins
Cyclic AMP
Hemodynamics
Adrenergic beta-Agonists
Nitric Oxide Synthase Type II
Septic Shock
Thoracic Aorta
Nitric Oxide Synthase
Free Radicals
Catecholamines
Lipopolysaccharides
Arginine

ASJC Scopus subject areas

  • Immunology

Cite this

Isoproterenol regulates tumour necrosis factor, interleukin-10, interleukin-6 and nitric oxide production and protects against the development of vascular hyporeactivity in endotoxaemia. / Szabo, Csaba; Haskó, G.; Zingarelli, B.; Németh, Z. H.; Salzman, A. L.; Kvetan, V.; Pastores, S. Mccarthy; Vizi, E. S.

In: Immunology, Vol. 90, No. 1, 1997, p. 95-100.

Research output: Contribution to journalArticle

Szabo, C, Haskó, G, Zingarelli, B, Németh, ZH, Salzman, AL, Kvetan, V, Pastores, SM & Vizi, ES 1997, 'Isoproterenol regulates tumour necrosis factor, interleukin-10, interleukin-6 and nitric oxide production and protects against the development of vascular hyporeactivity in endotoxaemia', Immunology, vol. 90, no. 1, pp. 95-100.
Szabo, Csaba ; Haskó, G. ; Zingarelli, B. ; Németh, Z. H. ; Salzman, A. L. ; Kvetan, V. ; Pastores, S. Mccarthy ; Vizi, E. S. / Isoproterenol regulates tumour necrosis factor, interleukin-10, interleukin-6 and nitric oxide production and protects against the development of vascular hyporeactivity in endotoxaemia. In: Immunology. 1997 ; Vol. 90, No. 1. pp. 95-100.
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AU - Németh, Z. H.

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AU - Kvetan, V.

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