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Published on: December 21, 2018
A Potential Mechanism for Immune Suppression by Beta-Adrenergic Receptor Stimulation following Traumatic Injury
Nicholas J Shubin1, Tam N Pham2, Kristan Lea Staudenmayer3
1Seattle Children's Research Institute, Seattle Children's Hospital, Seattle, Washington, USA.
Background:
β-Adrenergic agents suppress inflammation and may play an important role in posttraumatic infections. Mechanisms may include inhibition of MAP kinase signaling. We sought to determine whether MKP-1 contributed to catecholamine suppression of innate immunity and also wanted to know whether early catecholamine treatment after traumatic injury increases the risk of later nosocomial infection.
Methods:
We performed experiments using THP-1 cells and peripheral blood mononuclear cells from healthy individuals. We exposed cells to epinephrine and/or LPS and measured inflammatory gene transcription and MAP kinase activation. We inhibited MKP-1 activity to determine its role in catecholamine-induced immune suppression. Finally, we studied injured subjects to determine whether early catecholamine treatment was associated with nosocomial infection.
Results:
Epinephrine increases MKP-1 transcripts and protein and decreases LPS-induced p38 and JNK phosphorylation and TNF-α gene transcription. RNAi inhibition of MKP-1 at least partially restores LPS-induced TNF-α gene expression (p = 0.024). In the clinical cohort, subjects treated with β-adrenergic agents had an increased risk of ventilator-associated pneumonia (aOR = 1.9; 95% CI = 1.3-2.6) and bacteremia (aOR = 1.5; 95% CI = 1.1-2.3).
Conclusions:
MKP-1 may have a role in catecholamine-induced suppression of innate immunity, and exogenous catecholamines might contribute to nosocomial infection risk.
Insights
Beta-adrenergic agents, like epinephrine, may increase nosocomial infection risk by suppressing innate immunity via MKP-1. Early catecholamine treatment after trauma is linked to higher infection rates in patients.
Area of Science:
- Immunology
- Molecular Biology
- Trauma Research
Background:
- Beta-adrenergic agents can suppress inflammation, potentially influencing post-traumatic infections.
- Mechanisms may involve mitogen-activated protein (MAP) kinase signaling pathways.
- The role of MKP-1 in catecholamine-induced immune suppression and the risk of nosocomial infections after trauma require investigation.
Purpose of the Study:
- To determine if MKP-1 contributes to catecholamine-mediated suppression of innate immunity.
- To investigate whether early catecholamine treatment post-trauma elevates the risk of subsequent nosocomial infections.
Main Methods:
- Experiments utilized THP-1 cells and peripheral blood mononuclear cells exposed to epinephrine and lipopolysaccharide (LPS).
- Inflammatory gene transcription and MAP kinase activation were measured.
- MKP-1 activity was inhibited to assess its role in immune suppression.
- A clinical cohort of injured subjects was analyzed for associations between early catecholamine treatment and nosocomial infection.
Main Results:
- Epinephrine increased MKP-1 transcripts and protein, while decreasing LPS-induced p38/JNK phosphorylation and TNF-α transcription.
- Inhibition of MKP-1 partially restored LPS-induced TNF-α gene expression.
- Clinical data showed increased risks of ventilator-associated pneumonia and bacteremia in subjects treated with beta-adrenergic agents.
Conclusions:
- MKP-1 may play a role in catecholamine-induced innate immune suppression.
- Exogenous catecholamines could potentially increase the risk of nosocomial infections following traumatic injury.
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