Endotoxin - Product of some bacteria structure known to cause inflammation. Also known as lipopolysaccharide and abbreviated to LPS. Part of gram negative bacteria cell wall.
CD14 - A protein involved detection of endotoxin.
TLR4 - A protein involved detection of endotoxin.
TLR2 - A protein involved detection of endotoxin.
MyD88 - A protein involved detection of endotoxin.
NFKB - Protein involved in genetic transcription changes in response to stress.
LBP - Lipopolysaccharide binding protein. Binds endotoxin after detection.
The sequence of detection to inflammation is (partially)
TNF/TNFa > Inflammatory cytokine
IL-1b > Inflammatory cytokine linked to pain
IL-6 > An inflammatory cytokine and an anti-inflammatory myokine.
Il-8 > Inflammatory cytokine
iNOS > An enzyme catalysing the production of nitric oxide, induced by cytokines.
COX > Cyclooxygenase, a family of enzymes involved in the formation of prostaglandins.
Inflammation from endotoxin can cause lung problems either from inhalation or peripheral circulation. In cell models glycine can blunt increases in TNF-Alpha, superoxide, and intracellular calcium.
In rodent models dietary glycine lowers mortality from endotoxin and lowers tumour necrosis factor alpha. Glycine protects the lungs but not the liver from the damage due to endotoxin.
Endotoxin is thought to be causal in some types of asthma, in one analysis of serum amino acids glycine was strongly associated with lower risk for asthma.
In rodents injected with endotoxin, concurrent glutamine administration minimises the decrease in plasma glutamine and reduces the concentration of both proinflammatory and anti-inflammatory cytokines.
Glutamine increases heat shock protein and dramatically reduces mortality while protecting organs from endotoxin damage.
Glutamine attenuates lung damage from endotoxin.
Glutamine decreases TNFa, while increasing heat shock protein 72 in peripheral blood polymorphonuclear cells.
*Glutamine may not be suitable for frequent supplementation to lower low grade endotoxemia and inflammation, it’s perhaps best seen as an emergency treatment for sepsis.*
Zinc carnosine decreased mortality, plasma nitric oxide and TNFa after endotoxin administration. It also mitigated related lung damage and increase in nitric oxide. It’s thought to work by zinc inhibiting NFKB, no effects on heat shock protein were found.
Zinc carnosine increases gut repair, reduces stress induced gastric and small intestinal injury in rodents and prevents drug induced increases in permeability in humans.
Zinc deficiency is common in alcoholic liver disease. zinc supplementation protected rodents from alcohol induced GI permeability and liver damage.
Endotoxin administration increases circulating magnesium, higher magnesium status was strongly correlated with increased survival following endotoxin administration.
Magnesium sulfate decreased maternal TNFa and Il-6 and cytokine production in term and preterm neonates.