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PMID: 9294119 Published · ppublish English Journal Article

Beta2-agonists prevent Th1 development by selective inhibition of interleukin 12.

The Journal of clinical investigation ·Vol. 100 ·No. 6 ·1997-09-15 ·Pages 1513-9

Panina-Bordignon P, Mazzeo D, Lucia PD, D'Ambrosio D, Lang R, Fabbri L, Self C, Sinigaglia F

Abstract

Interleukin 12 (IL-12) plays a central role in the immune system by skewing the immune response towards T helper 1 (Th1) type responses which are characterized by high interferon-gamma and low IL-4 production. In this report we present evidence that beta2-agonists inhibit IL-12 production by both human monocytes in response to lipopolysaccharide (LPS) and dendritic cells stimulated via CD40. Inhibition of IL-12 production is selective, as other cytokines produced by monocytes are unaffected. IL-12 inhibition is dependent on beta2-adrenoceptor stimulation and correlates with increased levels of intracellular cAMP. In conjunction with their ability to suppress IL-12 production, when beta2-agonists are added at priming of neonatal T lymphocytes, they inhibit the development of Th1-type cells, while promoting T helper 2 (Th2) cell differentiation. Further, the in vivo administration of a therapeutic dose of salbutamol results in the selective inhibition of IL-12 production by whole blood lymphocytes stimulated in vitro with LPS. These findings provide new insight into the immunological consequences of the clinical use of beta2-agonists and may suggest new approaches for the treatment of Th1-mediated diseases.

MeSH Terms
Adrenergic beta-2 Receptor Agonists Adrenergic beta-2 Receptor Antagonists Adult Albuterol/pharmacology Bucladesine/pharmacology Cell Differentiation/drug effects Colforsin/pharmacology Cyclic AMP/metabolism Dendritic Cells/drug effects,metabolism Dose-Response Relationship, Drug Humans Interferon-gamma/pharmacology Interleukin-1/metabolism Interleukin-10/metabolism Interleukin-12/metabolism Interleukin-6/metabolism Lipopolysaccharides/pharmacology Macrophages/drug effects,metabolism Oxprenolol/pharmacology RNA, Messenger/analysis Th1 Cells/drug effects,metabolism Th2 Cells/drug effects,metabolism Tumor Necrosis Factor-alpha/metabolism
Chemicals
Adrenergic beta-2 Receptor Agonists Adrenergic beta-2 Receptor Antagonists Interleukin-1 Interleukin-6 Lipopolysaccharides RNA, Messenger Tumor Necrosis Factor-alpha Interleukin-10 Interleukin-12 Colforsin Oxprenolol Bucladesine Interferon-gamma Cyclic AMP Albuterol
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Panina-Bordignon P
Roche Milano Ricerche, I-20132 Milan, Italy.
Mazzeo D
Lucia P D
D'Ambrosio D
Lang R
Fabbri L
Self C
Sinigaglia F
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI119674
Published
1997-09-15
Pages
1513-9
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC508332
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI119674 PMC Full Text View journal details
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