I saw this earlier today..

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3592351/

Long article but informative..

Inflammation is the body's first line of defense against infection or injury, responding to challenges by activating innate and adaptive responses. Microbes have evolved a diverse range of strategies to avoid triggering inflammatory responses. However, some pathogens, such as the influenza virus and the Gram-negative bacterium Francisella tularensis, do trigger life-threatening “cytokine storms” in the host which can result in significant pathology and ultimately death. For these diseases, it has been proposed that downregulating inflammatory immune responses may improve outcome. We review some of the current candidates for treatment of cytokine storms which may prove useful in the clinic in the future and compare them to more traditional therapeutic candidates that target the pathogen rather than the host response.
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INTRODUCTION

In the event of tissue damage, whether caused by injury or infection, inflammation is the body's first coordinated line of defense. It is responsible for activating both innate and adaptive immune responses so that the damage can be resolved and homeostasis restored. The characteristic signs of inflammation include heat, redness, swelling, and pain and are easily recognizable (1). There are four stages to a classical self-limiting inflammatory response: (i) recognition of the problem, (ii) recruitment of leukocytes and other immune system components, (iii) elimination of the threat, and (iv) resolution of the inflammatory state (i.e., a return to homeostasis).
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RECOGNITION

In the case of infection, inflammation begins when the cells of the innate immune system recognize a pathogen-associated molecular pattern (PAMP) possessed by the invading organism. PAMPs are often an essential feature of the microbe and therefore are highly conserved, increasing recognition (2). The receptors on host phagocytic cells that recognize PAMPs are known as pattern recognition receptors (PRRs), of which there are several different categories. Soluble PRRs such as mannose binding lectin act as opsonins, preparing the microbe for phagocytosis (3). Intracellular PRRs, notably the Nod-like receptors (NLRs), are found in the cytosol for the detection of intracellular pathogens (4). Retinoic acid-inducible gene (RIG)-like receptors (RLRs) share a caspase recruitment domain (CARD) with NLRs and are mainly responsible for viral detection (5, 6). Transmembrane PRRs include the Toll-like receptors (TLRs) and C-type lectin receptors. Activation of a subset of NLRs, NLRP1, NLRP3, and NLRC4, induces the formation of a multiprotein complex called the inflammasome. Upon assembly, caspase proteins are cleaved from their proforms to an active state leading to the processing of interleukin-1β (IL-1β) and IL-18 (7).

Once the PRR is activated and ligand binding occurs, a signaling cascade is triggered, which results in expression of specific proinflammatory cytokines. Cytokines play a vital role throughout the four stages of inflammation. During the early phase of infection, these protein messenger molecules act as signals to the immune system, regulating the duration and gravity of the immune response to damage or infection. Depending upon the specific cytokine that has been secreted, their role can be to activate (proinflammatory) or dampen (anti-inflammatory) the host response. For example, stimulated TLRs induce proinflammatory cytokines, while the production of the anti-inflammatory cytokine IL-10 is important during the later stages of infection in controlling disease-induced tissue pathology (8). In the case of sterile inflammation caused by tissue damage, trauma, and ischemia, PRRs recognize certain host-specific molecules that are only released during cell injury or necrotic death, termed damage-associated molecular patterns (DAMPs). These molecules include heat shock proteins and high-mobility group box 1 (HMGB1) and are recognized in much the same way as PAMPs (9).
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RECRUITMENT

Once recognition has occurred and inflammation has been initiated, certain host cells begin to secrete chemokines. Chemokines are relatively small proteins with a molecular weight of less than 10 kDa which activate and mediate the migration of leukocytes to the site of infection or inflammation (10). Many different types of cells are able to secrete these chemotactic cytokines, including phagocytic cells such as macrophages and neutrophils, though endothelial cells are responsible for over half of all produced. Chemokines activate integrins and bind to intercellular adhesion molecules (ICAMs) (11). Subsequently, cells roll along the endothelium, up a chemokine gradient to the site of inflammation where they transmigrate through cell junctions into the damaged or infected tissue (10, 12).
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RESOLUTION

Following recruitment of immune cells to the site of inflammation, resolution of the damage begins. The cytokines induced by PAMPs and produced by leukocytes are proinflammatory cytokines and include tumor necrosis factor alpha (TNF-α), IL-6, and members of the IL-1 family, all of which have different proinflammatory roles. TNF-α and IL-1β induce vasodilation and permeability, allowing immune cells to reach the site of damage, while IL-β and IL-6 induce complement and opsonization (2). As well as mediating the inflammatory response, proinflammatory cytokines can affect the brain, inducing behavioral and physiological symptoms such as fever, nausea, and anorexia (13).
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RETURN TO HOMEOSTASIS

Throughout its activation, the inflammatory response must be regulated to prevent a damaging systemic inflammation, also known as a “cytokine storm.” A number of cytokines with anti-inflammatory properties are responsible for this, such as IL-10 and transforming growth factor β (TGF-β) (14). Each cytokine acts on a different part of the inflammatory response. For example, products of the Th2 immune response suppress the Th1 immune response and vice versa (15). Without the ability to resolve the inflammation, the collateral damage to surrounding cells has the potential to be catastrophic, resulting in sepsis and even death. However, if it is controlled correctly, inflammation can be resolved effectively, with little or no long-term damage to the host (16).
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PATHOGENS

Pathogens attempt to skew the response of the finely balanced immune system in order to evade immune responses and have evolved a diverse range of strategies to favor their own growth, survival, and replication. At one extreme, some pathogens have strategies to appear invisible to the immune system and thus fail to induce an effective immune response, while at the other extreme, other pathogenic organisms are capable of hyperstimulating the immune system, commonly known as a cytokine storm. This can prevent the clearance of infection and induce tissue damage (i.e., necrosis, a potentially fatal condition). Many reviews have focused on immune evasion as a means to establish infection (17), but the importance of cytokine storms in disease is only just becoming apparent.

Diverse pathogenic viruses (e.g., influenza A) and bacteria (e.g., Francisella tularensis) have been found to induce cytokine storms or hypercytokinemia (Fig. 1) (18–20). These pathogens disrupt the delicate balance of a suitable inflammatory response, tipping it from being beneficial to destructive by causing large amounts of positive feedback in immune cells and upregulation of proinflammatory markers, in particular cytokines TNF-α, IL-1β, IL-8, and IL-6.

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STIMULATING THE CHOLINERGIC ANTI-INFLAMMATORY PATHWAY

The cholinergic anti-inflammatory pathway uses the neurotransmitter acetylcholine (Ach) to interact specifically with α7 subunit of nicotinic acetylcholine (α7nAch) receptors on innate immune cells such as macrophages. These receptors are able to respond to Ach from a number of sources, including other immune cells and the vagus nerve, and their activation results in the suppression of proinflammatory cytokines. NF-κB, the main transcription factor for proinflammatory cytokines, is activated by PAMPs such as lipopolysaccharide (LPS) and triggers a pathway which results in the translocation of NF-κB and the transcription of proinflammatory genes. Stimulation of the vagus nerve can inhibit this pathway, downregulating the immune response and even reversing the symptoms of sepsis (50, 51).

It has been shown that direct electrical stimulation of the vagus nerve can substantially reduce the levels of LPS-induced TNF-α in both the liver and serum of rats (52), as well as inhibiting secondary sepsis cascades such as systemic coagulation (53), increasing the rates of survival in both cases. However, electrical stimulation of the nervous system in humans would be too invasive and risky to be considered a feasible treatment for sepsis and hypercytokinemia, and so pharmaceutical methods of activating the α7nAch receptor are currently being investigated.

Nicotine is a nonselective agonist of the α7Ach receptor and is able to suppress the production of proinflammatory cytokines by mimicking the binding of acetylcholine. It has been demonstrated that nicotine can selectively reduce the inflammatory response in a number of infection scenarios, including Legionella pneumophila (54) and Chlamydia pneumoniae (55) infection; however, it is highly unlikely that nicotine will ever be used clinically due to its toxicity, addictive nature, and lack of specificity.

GTS-21, also known as DMXB-A, is another selective α7Ach receptor agonist already undergoing clinical trials for schizophrenia and Alzheimer's disease (56–58). It produces the same inflammatory modulation as nicotine but is nontoxic, does not result in an addiction, and has no known side effects (59). GTS-21 significantly reduces TNF-α and the late mediator of sepsis, HMGB1, downregulates IFN-γ pathways, and prevents the LPS-induced suppression of IL-10 and STAT 3 mechanisms (60), all of which contribute to a significant increase in survival in murine sepsis (59). In 2011, GTS-21 underwent in vivo human trials for the treatment of sepsis. The effects of orally administered GTS-21 at the highest known safe dose were examined in response to endotoxin-induced sepsis. The effects, while clearly dose-dependent, were highly variable between subjects and the mean plasma concentration of GTS-21 was low, resulting in a lack of statistically significant results. Within each individual, however, low levels of IL-6 and TNF-α were observed, proportional to the GTS-21 plasma concentration, indicating that high doses or different methods of administration may produce a more significant effect (61). There may also be potential for other α7Ach receptor agonists such as CNI-1495, which has already been shown to increase survival in murine sepsis models (62, 63).

I think the coronavirus is biological warfare. I also wonder
: if you whack it with oil of oregano, C/S, zinc, garlic,
: echinacea, and vitamins D3 and C, if that will prevent it
: if you just get the symptoms, or cure it?

: With the laws today, is it even legal to post this? ;O)