The Sympathetic Control of Blood Supply Is Different in the Spleen and Lymph Nodes

Abstract

Objectives: The noradrenergic innervation of lymphoid organs controls several immune cell functions and local blood perfusion. Considering that cell and antigen uptake depend on the blood supply to lymphoid organs, the hypothesis was tested that feedback signals from activated immune cells control sympathetic vasomotor activity. Methods: We determined the blood flow in spleen and mesenteric lymph nodes (mLN) of Wistar Kyoto rats during immune stimulation with endotoxin (LPS; 10 µg/kg) and following disruption of the noradrenergic transmission. Results: Our data indicate that (a) the splenic noradrenaline content, which reflects the density of the sympathetic innervation, is 5 times higher in the spleen than in other peripheral organs and the spleen receives stronger tonic sympathetic input than mLN; (b) immune stimulation with LPS causes a 4-fold increase in the IL-1β production in the spleen, but only 2-fold in mLN; (c) IL-1β causes an inhibition of the sympathetic vasoconstrictor tonus in the spleen, but has no significant effect on the noradrenergic vascular tonus in mLN, and (d) in mLN, the local hyperemia induced by LPS is attenuated by the degranulation of vesicular stores of histamine and serotonin, indicating that these monoamines participate in the vasodilator effect of LPS in mLN. Conclusions: The present experiments, taken together with our previous studies, indicate that the control of blood supply to the spleen and mLN involves different mechanisms. While blood perfusion in the spleen depends on the inhibition of the noradrenergic vasoconstriction by endogenously produced IL-1β, other vasoactive mediators such as serotonin and histamine play a role in the control of mLN perfusion.

Hyperthermia-enhanced splenic cytokine gene expression is mediated by the sympathetic nervous system

“…However, this was not the case in the present study, as splenic BF responses to heating did not differ between splenic-intact and splenic-denervated rats. As demonstrated in a series of studies by Rogausch et al (53,54,55), splenic BF regulation in the rat involves complex mechanisms. In this regard, the current study provides little insight concerning the role of the sympathetic nervous system in modulating splenic BF responses to WBH; however, the primary focus of the blood flow studies was not to discern mechanisms regulating splenic BF responses to heating.…”

“…In addition, immune cell products can influence the functional state of the sympathetic nervous system. For example, Rogausch et al (53,54,55) demonstrated that locally produced IL-1␤ inhibits the release of norepinephrine from postganglionic splenic sympathetic nerves, which in turn leads to an increase in splenic blood flow (BF).…”

Ontogeny of Intrinsic Innervation in the Human Thymus and Spleen

“…Experimental studies have shown that the neuronal pathway is involved in the control of immune responsiveness at several levels, from cellular functions and interactions to overall immunological responses (Rogausch et al 2004, Wrona 2006. It seems that stimulation of the sympathetic nervous system results in localization of the inflammatory response, suppression of T1 helper-mediated responses (Vizi et al 1995;Friedman and Irwin 1997;Kurz et al 1997), and protection from the detrimental effects of pro-inflammatory cytokines (Hasko et al 1998;Elenkov et al 2000;Pavlov et al 2003).…”

Origins of the sympathetic innervation to the nasal-associated lymphoid tissue (NALT): An anatomical substrate for a neuroimmune connection

“…Sympathetic nerve fibers participate in the modulation of the local immune response acting at two different levels concurrently. Directly, by neurotransmitters interacting on their respective receptors present in immune competent cells (Kin and Sanders, 2006;Sanders, 2012) or indirectly, by regulating the blood flow in lymphoid compartments (Rogausch et al, 2004). Indeed, we found that VMAT2-ir nerve fibers run through NALT lymphoid cells but also innervates the intra-NALT blood vessels.…”