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

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 ?2-adrenoceptors of splenic regulatory lymphocytes to control systemic inflammation. Vagus nerve stimulation fails to control serum TNF levels in either ?2-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 ?2-agonists to control inflammation in both ?2-knockout and nude mice. ?2-Agonists inhibit cytokine production in splenocytes (IC(50)? 1 ?M) and prevent systemic inflammation in wild-type but not in ?2-knockout mice. ?2-Agonists rescue wild-type mice from established polymicrobial peritonitis in a clinically relevant time frame. Regulatory lymphocytes reestablish the anti-inflammatory potential of ?2-agonists to control systemic inflammation, organ damage, and lethal endotoxic shock in ?2-knockout mice. These results indicate that ?2-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.

SUBMITTER: Vida G 

PROVIDER: S-EPMC3236627 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature