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HDFx: A Stress-induced Biologic that Inhibits and Reverses Endotoxin-induced Fevers and Depression in Cardiac Hemodynamics in Rabbits, Guinea-pigs and Rats: Potential Relevance to Coronaviral Fevers and Role of NF-Kb

Burton M. Altura*, Phyllis M. Gootman , Asefa Gebrewold, Lee S. Mestel, Anthony Carella

All mammals and many vertebrates, including humans, develop fevers in the presence of numerous infectious microorganisms, such as bacteria, funguses, rickettsia,
and viruses. Many of the gram-negative bacteria, such as E. coli and S. enteriditis, produce fever via cell wall products called endotoxins which release
lipopolysaccharides (LPS). The initial LPS-induced fever phase, in rats, guinea-pigs, and rabbits, usually starts in 30-45 min after exposure to the pyrogen. In
experimental animals like rodents, the fevers can be carefully quantified by changing the dose of the LPS bacteria. Using such quantification, our laboratories (over more
than 50 yr) have quantified the various doses of both E. coli and S. enteriditis endotoxins in Wistar rats, guinea-pigs and New Zealand rabbits in order to gain some
insight into the mechanisms of the induced fevers and induction of death. As many others have reported, the endotoxin-pyrogens induce a release of numerous
cytokines (e.g., interleukin 1 beta, tumor necrosis factor, IL-6, among many others) which act on the hypothalamus to induce the fevers.Invasion of the body in rodents and humans after administration of endotoxins ( including contamination of foods with endotoxins) usually results in changes in cardiac
hemodynamics within 3-20 hrs . These alterations include reductions in coronary blood flows, reductions in left ventricular (LV) pressures, reductions in cardiac
contractility and falls in arterial blood pressure [for review, see 3]. With time and increasing dose, the endotoxins often lead to septic shock and multiple organ failure
which causes irreparable damage of the lungs, kidneys, liver and the cardiovascular system and death.While studying these mechanism of endotoxin- induced fevers, cardiac hemodynamics, and subsequent death, we noticed that surviving animals exhibited a
transferable 35-40 kD protein which we termed HDF. We found that transfer of crude extracts of HDFx to naïve ratsguinea-pigs, and rabbits, as well as mice and
piglets would induce protection against sublethal hemorrhage, intestinal ischemic shock, traumatic Injury, fungal infections, and centripetal forces [5,6, unpublished
findings]. In addition, we noted that HDFx possessed unique healing and regenerative properties.