Topic: 2007: How TNF was recognized as a key mechanism of disease
CaliforniaLyme
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They have just been developing a whole range of TNF inhibitor drugs!!! Some researchers see this as working for Lyme, some don't! This article mentions Babs. I had very high TNF levels- stands for Tumor Necrosis Factor. **********************************************
1: Cytokine Growth Factor Rev. 2007 Jun-Aug;18
How TNF was recognized as a key mechanism of disease.
Clark IA. School of Biochemistry and Molecular Biology, Australian National University, Canberra, ACT, Australia. [email protected]
This review summarizes the origins of the insight that excess production of pro-inflammatory cytokines caused a constellation of changes that contribute to pathophysiology of disease.
This connection was made following the original 1975 TNF (tumor necrosis factor) publication from New York describing how activated macrophages kill tumors.
The study caught the eye of a group in London who were trying to understand how the same in vivo macrophage activation would protect mice against the erythrocytic protozoan parasites that cause malaria and babesiosis.
Based on collaborative research between these two groups, it was argued in 1981 that TNF and related cytokines initiated events that caused pathology, as well as parasite death within red cells in these infectious diseases.
This proved to be a key conceptual advance. It was also argued that the pathology of bacterial sepsis logically had TNF origins.
Once TNF was cloned in 1985, allowing its specific analysis in serum and neutralization in vivo, the involvement of this cytokine in infectious disease pathology was pursued by a number of groups.
Some researchers found that once "their" cytokine was cloned and sequenced, they had been unwittingly expanding knowledge on TNF for several years.
By the late 1980s excess TNF production was proposed to be central to acute systemic viral diseases.
This family of cytokines is now at the centre of investigations to understand the mechanisms of acute systemic viral diseases, including influenza and the hemorrhagic viral diseases.
With its implication as the master regulator of other inflammatory cytokines in the synovial membrane, TNF has also become the major cytokine in the pathogenesis of chronic inflammatory disease. Its neutralization has proven to be a potent treatment for rheumatoid arthritis and Crohn's disease.
PMID: 17493863
-------------------- There is no wealth but life. -John Ruskin
All truth goes through 3 stages: first it is ridiculed: then it is violently opposed: finally it is accepted as self evident. - Schopenhauer Posts: 5639 | From Aptos CA USA | Registered: Apr 2005
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CaliforniaLyme
Frequent Contributor (5K+ posts)
Member # 7136
posted
1: Lancet. 1978 Jul 8;2(8080):75-7.
Does endotoxin cause both the disease and parasite death in acute malaria and babesiosis?
Clark IA.
When mice are infected with either of several species of Plasmodium or Babesia the amount of Escherichia coli lipopolysaccharide (L.P.S.) required to kill them is decreased several hundred fold.
The higher their parasitaemia the greater their susceptibility. There is indirect evidence that more L.P.S. than usual is present during infection with these parasites.
In a very susceptible host this may be sufficient to produce endotoxin shock. Non-antibody mediators able to kill rapidly dividing cells, which are released during endotoxin shock, may then control the parasitaemia of acute primary attacks.
This may explain why agents such as B.C.G., which produce responsiveness to abnormally low concentrations of L.P.S., protect against infection with certain of these parasities.
It may also explain why host species naturally resistance to L.P.S. become ill only at high parasite concentrations, and why others with a naturally high susceptibility to L.P.S. become ill when infected with relatively few parasites.
In the individual host convalescence from certain bacterial infections or concomitant infection with L.P.S.-producing organisms may vary the parasitaemia required to produce illness.
PMID: 78300
-------------------- There is no wealth but life. -John Ruskin
All truth goes through 3 stages: first it is ridiculed: then it is violently opposed: finally it is accepted as self evident. - Schopenhauer Posts: 5639 | From Aptos CA USA | Registered: Apr 2005
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