Sympathetic nerves control bacterial clearance

Abstract

A neural reflex mediated by the splanchnic sympathetic nerves regulates systemic inflammation in negative feedback fashion, but its consequences for host responses to live infection are unknown. To test this, conscious instrumented sheep were infected intravenously with live E. coli bacteria and followed for 48 h. A month previously, animals had undergone either bilateral splanchnic nerve section or a sham operation. As established for rodents, sheep with cut splanchnic nerves mounted a stronger systemic inflammatory response: higher blood levels of tumor necrosis factor alpha and interleukin-6 but lower levels of the anti-inflammatory cytokine interleukin-10, compared with sham-operated animals. Sequential blood cultures revealed that most sham-operated sheep maintained high circulating levels of live E. coli throughout the 48-h study period, while all sheep without splanchnic nerves rapidly cleared their bacteraemia and recovered clinically. The sympathetic inflammatory reflex evidently has a profound influence on the clearance of systemic bacterial infection.

Divergence of neuroimmune circuits activated by afferent and efferent vagal nerve stimulation in the regulation of inflammation

“…2020; Lankadeva et al . 2020; Ramirez et al . 2020 a , b ), to the inhibition of overexuberant immune responses (Borovikova et al .…”

Is the Sympathetic System Detrimental in the Setting of Septic Shock, with Antihypertensive Agents as a Counterintuitive Approach? A Clinical Proposition

“…Thus, surgical sympathectomy would lower IL-10 (Figure 2 in ref. [254]) and increase pathogen clearance, as in Figure 3 in ref. [254]).…”

“…In animals with cut splanchnic nerves, there was a stronger pro-inflammatory response, a faster resolution of the bacteremia, and more rapid recovery of the animals (higher plasma TNF and pro-inflammatory IL-6, lower anti-inflammatory IL-10; Figures 2 and 3 in ref. [254]). Here, early proinflammation is beneficial.…”

Emerging benefits and drawbacks of α2‐adrenoceptor agonists in the management of sepsis and critical illness

“…Catecholamines have also been shown to contribute to the formation of thromboses and microcirculatory abnormalities (De Backer et al, 2013) and to stimulate the growth of several gram‐positive and negative bacteria in vivo (Evans, Miles, & Niven, 1948). Furthermore, sympathetic overstimulation is accepted as a critical mediator of sepsis‐induced immunosuppression (Lankadeva, May, McKinley, et al, 2020; Martelli, Yao, McKinley, & McAllen, 2014) These findings have led to the suggestion that sympatholytic therapies may offer a degree of organ protection during sepsis (Andreis & Singer, 2016).…”

“…The pathophysiological mechanisms driving sepsis‐induced multi‐organ dysfunction syndrome remain to be fully elucidated. However, common pathophysiological features include inflammatory and sympathetic overactivity, vascular dysfunction, and microcirculatory abnormalities leading to regional organ‐specific tissue hypoxia and mitochondrial dysfunction (Andreis & Singer, 2016; Lankadeva et al, 2020; Lankadeva, Okazaki, Evans, Bellomo, & May, 2019; Ma et al, 2019; Spapen, Jacobs, & Honoré, 2017). Here, we will review the recent experimental research that illustrates how α 2 ‐adrenoceptor agonists can mitigate some of these pathological processes that mediate organ dysfunction in sepsis.…”