Coivd-19 patients have difficulty breathing. Is this due to lost of lung capacity, the cytokine storm, or a combination of the two? The neurons of the locus ceruleus are themselves very sensitive to CO2/pH.  The A6 norepinepthrine releasing neurons of the LC play a role in translating changes in CO2/pH to changes in respiration.  This post started asking if cytokines in the Covid-19 cytokine storm effect neurons in the locus ceruleus.
From the peritoneum to the brain
Borsody and Weiss(2005) followed up on previous studies that demonstrated that ip injection of microbial substances–
- lipopolysaccharide, peptidoglycan bacteria
- poly-inosine: poly-cytosine (poly(I):(C)) RNA viruses—
increased the spontaneous discharge rates and sensory-evoked responses of isolated locus coeruleus (LC) neurons in a dose- and time-related manner in rats. Complete transection of the subdiaphragmatic vagus nerves abolished this response. A variety of microbial substances excited LC neurons after administration into the peritoneal cavity in a manner involving the subdiaphragmatic vagus nerves. Perhaps these studies have ramifications of any bacterial or viral sepsis.
Both i.p. peptidoglycan and poly(I)/(C) increased LC activity but with lesser efficacy than LPS. Was this due to the inflammatory cytokine interleukin 1 (IL-1)? IL-1 receptor antagonists ( IL-1RA) reversed the increase in the activity of LC neurons caused by i.p. peptidoglycan treatment; however, that caused by i.p. Poly(I)/(C) was not diminished by IL-1RA. Thus, the increased activity of LC neurons caused by LPS and peptidoglycan requires IL-1 receptor binding, suggesting the involvement of endogenously-produced IL-1. In contrast, poly(I)/(C) increased the activity of LC neurons but this did not critically involve IL-1 receptors in the LC. .
Receptors for interleukin 2 are generally considered to be expressed in memory and regulatory T cells. The early 1990s saw interest in the neuro-immune axis. De Sarro and Nisticó injected recombinant human and rat IL-2 into the locus ceruleus of rat brains and measured electrical activity. . IL-2 injection caused slow wave sleep like patterns that were disrupted by agents that inhibit the heterotrimeric G protein signalling that is used by many cytokines receptors as well as cannabinoid receptors 
IL-6 in combination with IL-1
Ventricles of mice were injected with interleukin IL-1β (0.5 μg) and IL-6 (1 μg)  IL-1β and IL-6-dependent LC neuronal activation induced depression-like behavior and IL-1β induced increase in leptin levels enhanced α1-adrenoceptor-mediated depression-like behavior.
IL-7 and IL-10
Not addressed directly in the literature, i.e. PubMed searches.
IP-10 aka Cxcl 10
Cxcl-10 in an interferon gamma induced secreted protein that is a well established component of the Covid-19 cytokine storm.  Cxcl 10 has also been speculated to be responsible for loss of taste and smell in Covid-19 infections.
Granulocyte-macrophage colony-stimulating factor is being explored as a therapeutic target for Coivd-19 via antibodies against this secreted pro-inflammatory cytokine as well as its receptor . Myeloid cells activated by GM-CSF may secrete inflammatory cytokines IL-1 and IL-6 as well as reactive oxygen species.  IFNγ prevents secretion of GM-CSF and fatal HSV1 encephalitis caused by the invasion of the brain stem by inflammatory monocytes and neutrophils .
MCP-1, aka CCL2
(TNF-α), chemokine (C-C-motif) ligand 2 (CCL2), and granulocyte-macrophage colony-stimulating factor (GM-CSF). A recent review lists these cytokines as part of the COVID-19 cytokine storm: IL-6)\, IL-1β, TNF-α, GM-CSF, and CCL2.  The Kempurai does a nice job of reviewing the Covid-19 virus and the cytokine storm. Then the authors discuss locus ceruleus psychological aspects of Covid-19 such as
- tension that can increase shortness of breath
- sleeping disorders
- fear and anxiety
Another story found that patients with mood disorders or suicide attempt were more likely to be sero positive for Coivd-19 and influenza A and B viruses.  The effect of viral associated cytokines on expression of enzymes involved in serotonin synthesis was speculated to be be part of the iteology. 
Macrophage inflammatory protein (MIP-1) may also induce the secretion of IL-1, IL-6, and TNFα .
Keneko and coworkers  injected mice with lipopolysaccharide and found that this stimulated microglial cells to produce TNF-α. They also found that NE from the locus ceruleus suppressed this inflammatory response. The influence on respiration was not addressed.
H5N1 and ventilation
The highly pathogenic H5N1 (HK483) viral infection causes a depressed hypercapnic ventilatory response (dHCVR, 20% ↓) at 2 days post infection (dpi) and death at 7 dpi in mice The authors cited four centers of the ventilation in repose to hypoxia and/or elevated CO2
- Glomus cells in the carotid body. Viral nucleocapsid protein NP was not found at this site.
- NE secreting neurons in locus coeruleus (LC). These neurons are sensitive to local acidosis. Viral NP was found in 35% of tyrosine hydroxylase posititive neurons.
- In serotonergic neurons in the raphe nuclei, 10% of the tryptophan hydrolase expressing neurons were also positive for viral NP.
- The neurokinin 1 receptor (NK1R)-expressing neurons in the retrotrapezoid nucleus (RTN) are chemosensitive and responsible for HCVR. Viral NP was found in 20% of the neurons.
The authors asked whether the dHCVR became worse over the infection period with viral replication in these cells/neurons. Mice intra nasally inoculated with saline or the HK483 virus were exposed to hypercapnia for 5 min at 0, 2, 4, or 6 dpi, followed by immunohistochemistry to determine the expression of nucleoprotein of H5N1 influenza A (NP) alone ….
Mice lacking the used mice with a targeted deletion of the Recombinant activating gene 1 (Rag1−/− ) lack functioning T and B cells. They can mount an innate but not adaptive immune response against the H1N1 virus. A 2016 study out of the Karolinska Institute tested the hypothesis that the H1N1 virus could lead to narcolepsy like symptoms in immune compromised rats. These authors discussed the autoimmune like loss of orexin secreting neurons in the lateral hypothalamus and the possible role of the H1N1 vaccine.
When the nasal passages of the mice were inoculated with H1N1, sleep/wake disturbances followed in a few weeks.  These authors observed viral infection of the noradrenergic neurons of the locus ceruleus. 
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