Lipoproteins can bind lipopolysaccharide (LPS) and decrease LPS-stimulated
cytokine production. Lipoprotein(a) [Lp(a)] was as potent as low-density
lipoproteins (LDL) in inhibiting LPS-stimulated tumor necrosis factor synthesis
by human mononuclear cells. The kinetics of LPS inhibition by Lp(a) was similar
to that of LDL. This suggests that circulating Lp(a) may be an important factor
determining the amplitude of the response to LPS in humans.
The systemic toxicity of gram-negative sepsis is largely due to endotoxin,
a lipopolysaccharide (LPS) component of the outer membrane of gram-negative
bacteria. LPS stimulates the production of proinflammatory cytokines such as
tumor necrosis factor alpha (TNF) and interleukin-1, which in turn may induce
disseminated intravascular coagulation, hypotension, and renal, hepatic, and
cerebral damage
These guys were looking for a reason for lp(a) to be in the human body besides the obvious benefit of increased risk of heart disease. Peter at Hyperlipid makes a good argument for lp(a) being useful as sort of an emergency artery-repair patch. So maybe it's an anti-bacterial, anti-fungal artery-repair patch. The anti-endotoxin effect is attributed specifically to the lipoprotein fraction; the body might fail to clear small, dense ldl from circulation in a high carb, low fat diet in order to preserve the ability to counter endotoxin.
According to wikipedia, blocking tnf can increase danger of opportunistic infection from already present fungus, causing diseases like tuberculosis.
http://www.ncbi.nlm.nih.gov/pubmed/8662983
Tumor necrosis factor (TNF)-alpha inhibits insulin signaling through
stimulation of the p55 TNF receptor and activation of sphingomyelinase.
Tumor necrosis factor (TNF)-alpha plays a central role in the state of insulin resistance associated with obesity. It has previously been shown that one important mechanism by which TNF-alpha interferes with insulin signaling is through the serine phosphorylation of insulin receptor substrate-1 (IRS-1), which can then function as an inhibitor of the tyrosine kinase activity of the insulin receptor (IR). However, the receptors and the signaling pathway used by TNF-alpha that mediate the inhibition of IR activity are unknown. We show here that human TNF-alpha, which binds only to the murine p55 TNF receptor (TNFR), is as effective at inhibiting insulin-dependent tyrosine phosphorylation of IR and IRS-1 in adipocytes and myeloid 32D cells as murine TNF-alpha, which binds to both p55 TNFR and p75 TNFR. Likewise, antibodies that are specific agonists for p55 TNFR or p75 TNFR demonstrate that stimulation of p55 TNFR is sufficient to inhibit insulin signaling, though a small effect can also be seen with antibodies to p75 TNFR. Exogenous sphingomyelinase and ceramides, known to be formed by activation of p55 TNFR, inhibit IR and IRS-1 tyrosine phosphorylation and convert IRS-1 into an inhibitor of IR tyrosine kinase in vitro. Myeloid 32D cells expressing IR and IRS-1 are sensitive to this inhibition, but cells expressing IR and IRS-2 are resistant, pointing to an important difference in the biological function between IRS-1 and IRS-2. These data strongly suggest that TNF-alpha inhibits insulin signaling via stimulation of p55 TNFR and sphingomyelinase activity, which results in the production of an inhibitory form of IRS-1.
TNF seems to impair wound healing. A decrease in insulin signalling fits into that.
http://autoimmunenews.blogspot.com/2009/09/broken-bones-blame-it-on-autoimmune.html
Let's see; impairs wound healing. Fights infection (endotoxin)... doesn't sound like TNF is trying to hurt us. When does rheumatoid arthritis seem like a good idea? When the alternative is tuberculosis? Or some other infection?
Anti-inflammatory might not be the right word. Blocking TNF does that. Pre-inflammatory? Before TNF becomes necessary. Glycine, taurine, vitamin d, fish oil.
And pay attention to this guy;
http://coolinginflammation.blogspot.com/2009/03/enteroviruses-autoimmunity-diabetes.html
No comments:
Post a Comment