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β2-Adrenoreceptors of regulatory lymphocytes are essential for vagal neuromodulation of the innate immune system.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2011-08-16)
Gergely Vida, Geber Peña, Alexandre Kanashiro, Maria del Rocio Thompson-Bonilla, David Palange, Edwin A Deitch, Luis Ulloa
ABSTRACT

The nervous system is classically organized into sympathetic and parasympathetic systems acting in opposition to maintain physiological homeostasis. Here, we report that both systems converge in the activation of β2-adrenoceptors of splenic regulatory lymphocytes to control systemic inflammation. Vagus nerve stimulation fails to control serum TNF levels in either β2-knockout or lymphocyte-deficient nude mice. Unlike typical suppressor CD25(+) cells, the transfer of CD4(+)CD25(-) regulatory lymphocytes reestablishes the anti-inflammatory potential of the vagus nerve and β2-agonists to control inflammation in both β2-knockout and nude mice. β2-Agonists inhibit cytokine production in splenocytes (IC(50)≈ 1 μM) and prevent systemic inflammation in wild-type but not in β2-knockout mice. β2-Agonists rescue wild-type mice from established polymicrobial peritonitis in a clinically relevant time frame. Regulatory lymphocytes reestablish the anti-inflammatory potential of β2-agonists to control systemic inflammation, organ damage, and lethal endotoxic shock in β2-knockout mice. These results indicate that β2-adrenoceptors in regulatory lymphocytes are critical for the anti-inflammatory potential of the parasympathetic vagus nerve, and they represent a potential pharmacological target for sepsis.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Extract-N-Amp Tissue PCR Kit, sufficient for 100 extractions, sufficient for 100 amplifications
Sigma-Aldrich
Extract-N-Amp Tissue PCR Kit, sufficient for 1000 extractions, sufficient for 1000 amplifications

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