The Tetracyclines Protect Against Sepsis Independently Of Their Antibiotics Effects

haidut

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A remarkable study, which demonstrates that not all antibiotics have been created equal. Namely, the tetracycline family of antibiotics is strikingly protective against lethality from sepsis, and that protection is completely separate from their antibiotics effects. For example, the study demonstrated that pre-treatment with a puny single dose of doxycycline in a HED of 0.25 mg/kg (intraperitoneal route, so orally one would need ~0.4 mg/kg to achieve the same effects) resulted in 80%+ survival of the mice inoculated with sepsis-causing bacteria while 100% of the non-treated mice died within a week of sepsis development. Furthermore, treatment with doxycycline increased survival and accelerated lung recovery in animals infected with an influenza virus, which conclusively proves that the protective effects are not due to antibiotic effects of the chemical as viruses are "immune" to antibiotic treatments. Doxycycline worked both when given a few hours before sepsis took hold and also when given for 3 consecutive days post-infection.

Host-dependent induction of disease tolerance to infection by tetracycline antibiotics
Portugal: Researchers discover group of antibiotics which can protect against sepsis

"...A team of Portuguese researchers has discovered that a certain group of antibiotics also provides protection against sepsis, in addition to helping in the direct control of the infection, by raising the possibility of their use as adjuvant treatments. In a study published Wednesday in the medical journal ‘Immunity’, the researchers concluded that tetracyclines (broad spectrum antibiotics) partially inhibit the activity of cell mitochondria and, in doing so, induce a compensatory response by the body that decreases tissue damage during an infection, such as sepsis, which results from a generalised infection and is characterised by triggering a deregulated immune response, which causes about 11 million deaths per year worldwide and for which there is no specific treatment."

"...In their observations, the researchers found that doxycycline, an antibiotic of the tetracycline family, gives an increase in the survival capacity of sepsis in mice, regardless of its effects on the bacterial load. According to Henrique Colaço, the other author of the study, these benefits extend to the lungs, with a decrease in cell damage and the activation of tissue repair mechanisms. “In addition, in the liver there is activation of stress response and metabolic changes that foster tissue protection”.
 

yerrag

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I got here on a search of tetracycline, as I'm thinking of using it to help lower my blood pressure.

I've done twelve weeks of antibiotics last year (doxy for 2 weeks, augmentin for 3, and azithromycin for 7. It failed to lower my bp, and I now know why.

My high bp exists because my plaque contains biofilm of periodontal bacteria mainly in a symbiotic synergistic blend of bacteria that has strong survival mechanisms. There is a constant release of bacteria that elicits an immune response. But because a bacteria in this colony can turn hydrogen peroxide into water using its catalase enzyme, the immune system never truly kills this bacteria, so the immune system in constantly trying but always failing to kill the bacteeria significantly.

In the process though, a lot of inflammation occurs and a lot of oxidative stress happens, from spillover ROS of phagycytosis to production of inflammatory cytokines. But because the blood has albumin and albumin is an effective antioxidant (because of the cysteine34 molecule which turns sulfhydryl bonds to disulfide bonds as it acts as an antioxidant), the oxidative stress is neutralized very well and no tissue destruction occurs.

However, this is a constant drain on the blood's store of albumin, and the lower albumin content of blood results in lower plasma volume (albumin attracts salt, and salt attracts more water to form plasma), and this results in lower blood volume. This lower blood volume requires the body to compensate by increasing blood pressure to ensure blood continues to be circulated thoroughly around the body and my tissues and organs are supplied with nutrients and their metabolic waste is transported out and detoxed.

This adaptation by the body is well and good. And I have just shown why high blood pressure is protective, at least in the context I just described.

However, the biofilm (along with the plaque of oxidized LDL and the foam cells in a necrotic core that resides between the intima and media of blood vessels) is a conditonal bomb that would explode at an opportune time. At some point when my immune system weakens, or when my albumin stores are not replaced as quickly as it is now, or when the plaque loosens because the media is becoming more fragile and the media starts to deteriorate (in old age), the bacteria will just stream out of the necrotic core and overwhelm the body's internal defenses. I think this is what's called sepsis, as the literature doesn't seem to want to elucidate on the subject of sepsis.

But I want to get rid of the plaque and the biofilm in me, and I want the high blood pressure condition to go away.

I've been able to lyse plaque in two ways so far, and each time my blood pressure would increase, and as you may have guessed, it's because more bacteria is being released when I either use systemic proteolytic enzymes or when I use a policosanol-cyclodextrin-high gamma vitamin E blend.

So, I'm thinking of antibacterial solutions that will complement well with my immune system. They both will destroy bacteria, but the antibiotic would lessen the load on the neutrophils, so that less phagoxytosis occurs, so that less spillover ROS is released, so that less albumin is used as an antioxidant to counter spillover ROS. I have tried taking vitamin C and NAC to see if they can reduce the use of albumin as an antioxidant, but their effects have been negligible. So my recourse now is to find effective antibiotics or antibacterials (herbal or chemical) as part of a stack that incorporates my vitamin E blend and/or proteolytic enzymes.

I think that if I can slowly rid of my blood vessels of plaque and the bacteria it harbors, I will be able to lower my blood pressure significantly, my blood circulation will definitely improve, and since a load is lifted off my back, my body will be able to concentrate more on producing energy that can be used for developmental purposes, rather than for problem-solving fire-fighting purposes. And lastly, it will keep me from dying of sepsis in my death bed.

I'm currently using methylene blue and have some success, although I have to stop taking my vitamin E blend to slow down the release of bacteria from the plaque being lysed. Still not sure whether I can take mb concurrently with the vitamin E blend, or whether I should pulse-dose them by alternating their use.

I'm also considering using cocoa butter, applied as a suppository multiple times over a day. Bypassing the oral intake, the stomach, and the liver first pass would enable more of the cocoa butter to get to my blood stream, and since saturated fat is also an antibiotic, it may work. I could also add haidut's deFibron to the cocoa butter. but I don't know if this would be redundant.

If these antibacterials are not effective the way I want them to be, then I would resort to using tetracycline as a start, and see where this takes me. I can buy tetracyline HCl or oxytextracyline in bulk easily. The problem here is that my treatment would last a minimum of 3 months to adequately remove the plaque that's accumulated over the years at a slow enough pace. Slow and steady is the way to go as to rush it would mean chunks of plaque could fall off and cause vessel blockages that only rushing me to an ER and subsequently a stay at the ICU would fix. And that would set me back in so many ways.
 

cedric

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Abstract​

Three tetracyclines (tetracycline, doxycycline, and minocycline) were found to possess iron-chelating activity
 

yerrag

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A remarkable study, which demonstrates that not all antibiotics have been created equal. Namely, the tetracycline family of antibiotics is strikingly protective against lethality from sepsis, and that protection is completely separate from their antibiotics effects. For example, the study demonstrated that pre-treatment with a puny single dose of doxycycline in a HED of 0.25 mg/kg (intraperitoneal route, so orally one would need ~0.4 mg/kg to achieve the same effects) resulted in 80%+ survival of the mice inoculated with sepsis-causing bacteria while 100% of the non-treated mice died within a week of sepsis development. Furthermore, treatment with doxycycline increased survival and accelerated lung recovery in animals infected with an influenza virus, which conclusively proves that the protective effects are not due to antibiotic effects of the chemical as viruses are "immune" to antibiotic treatments. Doxycycline worked both when given a few hours before sepsis took hold and also when given for 3 consecutive days post-infection.

Host-dependent induction of disease tolerance to infection by tetracycline antibiotics
Portugal: Researchers discover group of antibiotics which can protect against sepsis

"...A team of Portuguese researchers has discovered that a certain group of antibiotics also provides protection against sepsis, in addition to helping in the direct control of the infection, by raising the possibility of their use as adjuvant treatments. In a study published Wednesday in the medical journal ‘Immunity’, the researchers concluded that tetracyclines (broad spectrum antibiotics) partially inhibit the activity of cell mitochondria and, in doing so, induce a compensatory response by the body that decreases tissue damage during an infection, such as sepsis, which results from a generalised infection and is characterised by triggering a deregulated immune response, which causes about 11 million deaths per year worldwide and for which there is no specific treatment."

"...In their observations, the researchers found that doxycycline, an antibiotic of the tetracycline family, gives an increase in the survival capacity of sepsis in mice, regardless of its effects on the bacterial load. According to Henrique Colaço, the other author of the study, these benefits extend to the lungs, with a decrease in cell damage and the activation of tissue repair mechanisms. “In addition, in the liver there is activation of stress response and metabolic changes that foster tissue protection”.
I didn't go read the link, but since you did, do you think the researchers were within reason to conclude that the tetracylines' effect on sepsis were independent of their antibiotic effects? How were they able to make this conclusion?

Why wouldn't the antibiotics curtailing the growth of bacteria causing sepsis not be the sole reason for protection from sepsis? And let's say it's not the sole reason, how could they say the protection is mainly outside the antibiotic effects? If their reasoning is because a viral condition was alleviated by the use of antibiotics, it is faulty because a viral infection does not preclude having a bacterial infection together with it. A lot of times, a viral infection becomes a vector for bacterial infection. The viral infection weakens the host's immunity, and the bacteria being opportunistic, takes advantage of the host's weakened immune system to create a bacterial infection.

the researchers concluded that tetracyclines (broad spectrum antibiotics) partially inhibit the activity of cell mitochondria and, in doing so, induce a compensatory response by the body that decreases tissue damage during an infection, such as sepsis, which results from a generalised infection and is characterised by triggering a deregulated immune response
Or the tissue damage was decreased because the oxidative stress was lessened as there were less spillover ROS from less phagocytic action by neutrophils - because the antibiotics lessened the need for a strong immune response. These researcher are engaged in creating a Rube Goldberg machine when there is a simpler explanation, and seeks to go into abstractions that cannot be understood but sounds very sciency, as it would appear to be when the audience gets lost in their circular logic.

I cannot understand what they really mean by "inhibit the activity of cell mitochondria and, in doing so, induce a compensatory response by the body that decreases tissue damage." What exactly is the compensatory response? I doubt at all they elaborated on that, but I could be wrong, but it is often the case they leave the reader hanging on a thread.
 

yerrag

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Abstract​

Three tetracyclines (tetracycline, doxycycline, and minocycline) were found to possess iron-chelating activity
Thanks. It looks interesting and I shall dive into it!
 

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