Evidence that interferon-γ alters pineal metabolism both indirectly via sympathetic nerves and directly on the pinealocytes

Following an immune challenge, there is two-way communication between the nervous and immune systems. It is proposed that a neural reflex—the inflammatory reflex—regulates the plasma levels of the key proinflammatory cytokine TNF-α, and that its efferent pathway is in the splanchnic sympathetic nerves. The evidence for this reflex is based on experiments on anesthetized animals, but anesthesia itself suppresses inflammation, confounding interpretation. Here, we show that previous section of the splanchnic nerves strongly enhances the levels of plasma TNF-α in conscious rats 90 min after they received intravenous LPS (60 μg/kg). The same reflex mechanism, therefore, applies in conscious as in anesthetized animals. In anesthetized rats, we then determined the longer-term effects of splanchnic nerve section on responses to LPS (60 μg/kg iv). We confirmed that prior splanchnic nerve section enhanced the early (90 min) peak in plasma TNF-α and found that it reduced the 90-min peak of the anti-inflammatory cytokine IL-10; both subsequently fell to low levels in all animals. Splanchnic nerve section also enhanced the delayed rise in two key proinflammatory cytokines IL-6 and interferon γ. That enhancement was undiminished after 6 h, when other measured cytokines had subsided. Finally, LPS treatment caused hypotensive shock in rats with cut splanchnic nerves but not in sham-operated animals. These findings demonstrate that reflex activation of the splanchnic anti-inflammatory pathway has a powerful and sustained restraining influence on inflammatory processes.

Download Full-text

Clinical and Immune Responses of Peripheral Chemical Sympathectomy in Enterovirus 71 Infection

Frontiers in Immunology ◽

10.3389/fimmu.2021.700903 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yu-Ting Liao ◽

Huey-Pin Tsai ◽

Shih-Min Wang ◽

Shun-Hua Chen

Keyword(s):

Nervous System ◽

Immune Responses ◽

Plasma Levels ◽

Mononuclear Cells ◽

Enterovirus 71 ◽

Sympathetic Nerves ◽

Interferon Γ ◽

Chemical Sympathectomy ◽

Peripheral Blood Mononuclear ◽

The Absolute

The activation of the sympathetic nervous system, release of norepinephrine (NE), and adrenergic receptor signaling participate in and regulate the complicated enterovirus 71 (EV71) brainstem encephalitis (BE). The neurotoxin 6-hydroxydopamine (6-OHDA) selectively ablates sympathetic nerves and markedly depletes NE in innervated organs. Changes in the plasma levels of NE, severity score, cytokine profiles, and percentages of immunophenotype expression in 7-day-old Bltw : CD1 (ICR) mice infected with EV71, with or without 6-OHDA treatment, were compared. The survival rate (76.9%) of EV71-infected and 6-OHDA (30 μg/g)-treated mice was increased significantly. The clinical scores were decreased markedly on days 8-12 in MP4-infected and 6-OHDA-treated mice compared to those without treatment. The results showed that the plasma levels of NE, epinephrine, and dopamine were decreased on days 4–8 after 6-OHDA treatment and at most on day 8. The plasma levels of interleukin (IL)-12p70, tumor necrosis factor, IL-6, and IL-10 did not change significantly after 6-OHDA treatment. Interferon-γ levels decreased evidently on days 4, 6, and 8 after 6-OHDA treatment. The absolute events of CD3+CD4+, CD3+CD8+, and CD3+NK1.1+ cells of peripheral blood mononuclear cells were increased significantly in MP4-infected and 6-OHDA-treated mice compared to those without treatment. In splenocytes, the absolute cells of CD3−NK1.1+, CD3+NK1.1+ and CD11b+Gr-1+ cells of EV71-infected mice were increased significantly after 6-OHDA treatment. These findings suggested that 6-OHDA may be used a probe to explore clinical improvements and immune responses in the complicated EV71 infection. Taken together, peripheral chemical sympathectomy contribute to further understand the immunopathogenesis of EV71 BE with autonomic nervous system dysregulation.

Download Full-text

Human Neurofibromas in Co-Culture with Mouse Neurons

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053632 ◽

1982 ◽

Vol 40 ◽

pp. 194-195

Author(s):

R.L. Martuza ◽

T. Liszczak ◽

A. Okun ◽

T-Y Wang

Keyword(s):

Schwann Cell ◽

Schwann Cells ◽

Genetic Disorder ◽

Cranial Nerves ◽

Sympathetic Nerves ◽

Acoustic Neuromas ◽

Spinal Roots ◽

Neural Crest Origin ◽

Multiple Abnormalities ◽

Other Neoplasms

Neurofibromatosis (NF) is an autosomal dominant genetic disorder with a prevalence of 1/3,000 births. The NF mutation causes multiple abnormalities of various cells of neural crest origin. Schwann cell tumors (neurofibromas, acoustic neuromas) are the most common feature of neurofibromatosis although meningiomas, gliomas, and other neoplasms may be seen. The schwann cell tumors commonly develop from the schwann cells associated with sensory or sympathetic nerves or their ganglia. Schwann cell tumors on ventral spinal roots or motor cranial nerves are much less common. Since the sensory neuron membrane is known to contain a mitogenic factor for schwann cells, we have postulated that neurofibromatosis may be due to an abnormal interaction between the nerve and the schwann cell and that this interaction may be hormonally modulated. To test this possibility a system has been developed in which an enriched schwannoma cell culture can be obtained and co-cultured with pure neurons.

Download Full-text