Vagotomy Induces Deregulation of the Inflammatory Response during the Development of Amoebic Liver Abscess in Hamsters

Abstract

Background: The parasympathetic nervous system modulates the immune response in the abdominal-pelvic gut through the vagus nerve, which releases acetylcholine. This endogenous ligand acts on a7 nicotinic receptors expressed on immune cells. Objective: To study the mechanism of the production and regulation of cytokines in parasympathectomized and control hamsters during the development of amoebic liver abscesses (ALA) caused by Entamoeba histolytica.Methodology: Six- to 8-week-old male hamsters with and without vagotomy were used in a model of ALA. The animals were infected with trophozoites (350,000; HM1:IMSS strain) via the intrahepatic route and sacrificed at 6, 12, and 24 h and at 2, 4, and 7 days postinfection. Immune parameters were recorded at each time point using morphometric techniques including immunofluorescence and immunohistochemistry assays. These parameters included signal transducer and activator of transcription 3 (STAT3) levels, pro- and anti-inflammatory cytokine levels, and nuclear factor-γB (NFγB) activation in neutrophils and macrophages. Results: Compared to the control groups, the vagotomized (VAG) hamsters showed a significant increase in NFγB activation in neutrophils and macrophages, and higher levels of interleukin (IL)-1ß, IL-6, interferon-γ, and tumor necrosis factor-a. VAG hamsters showed an increase in the expression of IL-8 and phosphorylated STAT3 during the first 24 h postinfection as well as slightly increased levels of transforming growth factor-ß on days 2-7 postinfection. No significant differences were demonstrated in the levels of IL-10. Conclusions: These results suggest that the vagus nerve plays an important role in the regulation of inflammation during ALA formation.

Prevention of Burn-Induced Inflammatory Responses and Muscle Wasting by GTS-21, a Specific Agonist for α7 Nicotinic Acetylcholine Receptors

“…Though the precise reason about this result is unclear, this observation might be because of secondary effect through suppression of systemic and local inflammation. The effect of α7AChRs on anti-inflammatory cytokines is controversial (24, 26, 34). Further study is required to elucidate the involvement of α7AChRs in anti-inflammatory cytokines release and their effects on muscle mass loss and/or recovery.…”

Adrenergic regulation during acute hepatic infection withEntamoeba histolyticain the hamster: involvement of oxidative stress, Nrf2 and NF-KappaB

“…In addition, in a previous study [ 1 ], we reported that at this time, the increase in oxidative stress is greatest and the NF-κB pro-inflammatory pathway is activated. Moreover, the effect of the SNS and PNS during the early and late stages of amebic infection has also begun to be studied [ 3 , 42 , 51 ], but there is little knowledge on their participation and their relationship with the oxidative stress that is generated during the first hours of amebic infection. In 2011, Muñoz-Ortega [ 41 ] reported that liver parasympathectomy resulted in a larger ALA size, and a greater production of collagen fibers, causing an increase in the response against infection.…”

“…The CNS has been reported to regulate the immune system through two pathways: first, hormonal response, including the hypothalamic-pituitary-adrenal axis, as well as the hypothalamic-pituitary-gonadal, the hypothalamic-pituitary-thyroid and the hypothalamic-growth-hormone axes; and second, the autonomic nervous system through the release of norepinephrine and acetylcholine from sympathetic and parasympathetic nerves [ 15 ]. Due to these observations, researchers have begun to study the involvement of the autonomic nervous system during the inflammatory response induced by E. histolytica, suggesting that the sympathetic and parasympathetic nervous systems (SNS, PNS, respectively) modify immune response to amebic infection, inducing deregulation of pro-inflammatory proteins, such as NF-κB [ 3 , 41 , 51 ]. Moreover, recently we demonstrated that during the acute phase of ALA, the pro-inflammatory system of NF-κB is activated while the host antioxidant system of Nrf2 is decreased, inducing uncontrolled inflammation and oxidative stress.…”

The Involvement of Parasympathetic and Sympathetic Nerve in the Inflammatory Reflex

“…Following nAChRα7 activation in macrophages and endothelial cells, a series of intracellular signaling changes may occur. ACh released by the vagus nerve or other commercial drugs such as nicotine and nAChRα7 agonists inhibit IkB phosphorylation and subsequent transcriptional activity of NFkB on the TNFα promoter of the DNA (Sanchez‐Aleman et al, ). Nicotine reduced nuclear translocation of NFkB in endothelial cells induced by TNFα and increased cytoplasmic levels of IkB α and ϵ. Nicotine stimulation blocked cell activation and leukocyte recruitment during the inflammatory process.…”