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Open Access Research article

MAPK-dependent regulation of IL-1- and β-adrenoreceptor-induced inflammatory cytokine production from mast cells: Implications for the stress response

David S Chi1*, S Matthew Fitzgerald1, Shannon Pitts1, Karen Cantor1, Ellis King1, Steven A Lee1, Shau-Ku Huang2 and Guha Krishnaswamy1

Author Affiliations

1 Department of Internal Medicine, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee 37614, USA

2 The Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224, USA

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BMC Immunology 2004, 5:22  doi:10.1186/1471-2172-5-22

Published: 21 September 2004

Abstract

Background

Catecholamines, such as epinephrine, are elaborated in stress responses, and mediate vasoconstriction to cause elevation in systemic vascular resistance and blood pressure. Our previous study has shown that IL-1 can induce mast cells to produce proinflammatory cytokines which are involved in atherogenesis. The aim of this study was to determine the effects of epinephrine on IL-1-induced proatherogenic cytokine production from mast cells.

Results

Two ml of HMC-1 (0.75 × 106 cells/ml) were cultured with epinephrine (1 × 10-5 M) in the presence or absence of IL-1β (10 ng/ml) for 24 hrs. HMC-1 cultured alone produced none to trace amounts of IL-6, IL-8, and IL-13. IL-1β significantly induced production of these cytokines in HMC-1, while epinephrine alone did not. However, IL-6, IL-8, and IL-13 production induced by IL-1β were significantly enhanced by addition of epinephrine. The enhancing effect appears to involve NF-κB and p38 MAPK pathways. Flow cytometry showed the presence of β1 and β2 adrenoreceptors on resting mast cells. The enhancing effect of proatherogenic cytokine production by epinephrine was down regulated by the β1 and β2 adrenoceptor antagonist, propranolol, but not by the β1 adrenoceptor antagonist, atenolol, suggesting the effect involved β2 adrenoceptors. The enhancing effect of epinephrine on proatherogenic cytokine production was also down regulated by the immunosuppressive drug, dexamethasone.

Conclusions

These results not only confirm that an acute phase cytokine, IL-1β, regulates mast cell function, but also show that epinephrine up regulates the IL-1β induction of proatherogenic cytokines in mast cells. These data provide a novel role for epinephrine, a stress hormone, in inflammation and atherogenesis.