Recovery period of Ironman triathlon associated with significantly increased inflammatory response. The vast majority is resolved by day 5 in this study, though low-grade inflammation persisted beyond day 5. Cortisol was significantly elevated and Testosterone was significantly decreased in the early recovery period. Muscle damage and significant inflammation is a prominent finding in the recovery phase of a triathlon.
insulin, in women with PCOS, promotes increased 5-alpha reductase activity. This results in a dysregulated HPA axis, promoting increased cortisol and androgen levels.
hyperactive HPA axis associated with depression. This is becoming evident in the literature. This study looked at SNPS in the etiology of elevated cortisol and/or androstenedione. They followed the results with saliva and found that 3 SNPS were associated with increased 11Beta-HSD1 activity and associated increased depression.
The starting point for innate immunity activation is the recognition of conserved structures of bacteria, viruses, and fungal
components through pattern-recognition receptors
TLRs are PRRs that recognize microbe-associated molecular patterns
TLRs are transmembrane proteins containing extracellular domains rich in leucine repeat sequences and a cytosolic domain
homologous to the IL1 receptor intracellular domain
The major proinflammatory mediators produced by the TLR4 activation in response to endotoxin (LPS) are TNFα, IL1β and IL6,
which are also elevated in obese and insulin-resistant patients
Obesity,
high-fat diet, diabetes, and NAFLD are associated with higher gut permeability leading to metabolic endotoxemia.
Probiotics,
prebiotics, and antibiotic treatment can reduce LPS absorption
LPS promotes hepatic insulin
resistance, hypertriglyceridemia, hepatic triglyceride accumulation, and secretion of pro-inflammatory cytokines promoting
the progression of fatty liver disease.
In the endothelium, LPS induces the expression of pro-inflammatory, chemotactic, and
adhesion molecules, which promotes atherosclerosis development and progression.
In the adipose tissue, LPS induces adipogenesis,
insulin resistance, macrophage infiltration, oxidative stress, and release of pro-inflammatory cytokines and chemokines.
the gut microbiota has been recently proposed to be an environmental factor involved
in the control of body weight and energy homeostasis by modulating plasma LPS levels
dietary fats alone might not be sufficient to cause overweight and obesity, suggesting that a
bacterially related factor might be responsible for high-fat diet-induced obesity.
This was accompanied in high-fat-fed mice by a change in gut microbiota composition, with reduction in
Bifidobacterium and Eubacterium spp.
n humans, it was also shown that meals with high-fat and high-carbohydrate content (fast-food style western diet) were able
to decrease bifidobacteria levels and increase intestinal permeability and LPS concentrations
it was demonstrated that, more than the fat amount, its composition was a critical modulator of ME (Laugerette et al. 2012). Very recently, Mani et al. (2013) demonstrated that LPS concentration was increased by a meal rich in saturated fatty acids (SFA), while decreased after a
meal rich in n-3 polyunsaturated fatty acids (n-3 PUFA).
this effect seems to be due to the fact that some SFA (e.g., lauric and mystiric acids) are part of the lipid-A component
of LPS and also to n-3 PUFA's role on reducing LPS potency when substituting SFA in lipid-A
these experimental results suggest a pivotal role of CD14-mediated TLR4 activation in the development of
LPS-mediated nutritional changes.
This suggests a link between gut microbiota, western diet, and obesity and indicates that gut microbiota manipulation can
beneficially affect the host's weight and adiposity.
endotoxemia was independently
associated with energy intake but not fat intake in a multivariate analysis
in vitro that endotoxemia activates pro-inflammatory cytokine/chemokine production via NFκB and MAPK signaling in preadipocytes and
decreased peroxisome proliferator-activated receptor γ activity and insulin responsiveness in adipocytes.
T2DM patients have mean values of LPS that are 76% higher than healthy controls
LPS-induced release of glucagon, GH and cortisol, which inhibit glucose uptake, both
peripheral and hepatic
LPSs also seem to induce ROS-mediated apoptosis in pancreatic cells
Recent evidence has been linking ME with dyslipidemia, increased intrahepatic triglycerides, development, and progression
of alcoholic and nonalcoholic fatty liver disease
The hepatocytes, rather than hepatic macrophages, are the cells responsible for its clearance, being ultimately excreted
in bile
All the subclasses of plasma lipoproteins can bind and neutralize the toxic effects of LPS, both in vitro (Eichbaum et al. 1991) and in vivo (Harris et al. 1990), and this phenomenon seems to be dependent on the number of phospholipids in the lipoprotein surface (Levels et al. 2001). LDL seems to be involved in LPS clearance, but this antiatherogenic effect is outweighed by its proatherogenic features
LPS produces hypertriglyceridemia by several mechanisms, depending on LPS concentration. In animal models, low-dose LPS increases
hepatic lipoprotein (such as VLDL) synthesis, whereas high-dose LPS decreases lipoprotein catabolism
When a dose of LPS similar to that observed in ME was infused in humans, a 2.5-fold increase in endothelial lipase was observed,
with consequent reduction in total and HDL. This mechanism may explain low HDL levels in ‘ME’ and other inflammatory conditions
such as obesity and metabolic syndrome
It is known that the high-fat diet and the ‘ME’ increase intrahepatic triglyceride accumulation, thus synergistically contributing
to the development and progression of alcoholic and NAFLD, from the initial stages characterized by intrahepatic triglyceride
accumulation up to chronic inflammation (nonalcoholic steatohepatitis), fibrosis, and cirrhosis
On the other hand, LPS activates Kupffer cells leading to an increased production of ROS and pro-inflammatory cytokines
like TNFα
high-fat diet mice presented with ME, which
positively and significantly correlated with plasminogen activator inhibitor (PAI-1), IL1, TNFα, STAMP2, NADPHox, MCP-1, and
F4/80 (a specific marker of mature macrophages) mRNAs
prebiotic administration reduces intestinal permeability
to LPS in obese mice and is associated with decreased systemic inflammation when compared with controls
Cani et al. also found that high-fat diet mice presented with not only ME but also higher levels of inflammatory markers, oxidative
stress, and macrophage infiltration markers
This suggests that important links between gut microbiota, ME, inflammation, and oxidative stress are implicated in a high-fat
diet situation
high-fat feeding is associated with adipose
tissue macrophage infiltration (F4/80-positive cells) and increased levels of chemokine MCP-1, suggesting a strong link between
ME, proinflammatory status, oxidative stress, and, lately, increased CV risk
LPS has been shown to promote atherosclerosis
markers of systemic inflammation such as circulating bacterial endotoxin
were elevated in patients with chronic infections and were strong predictors of increased atherosclerotic risk
As a TLR4 ligand, LPS has been suggested to induce atherosclerosis development and progression, via a TLR4-mediated inflammatory
state.
It is now well recognized
that the disease manifestation is reduced in pregnant women with
relapsing-remitting MS
This occurs particularly during the
third trimester when levels of estrogens (estradiol and estriol) and
progesterone (see Table 2) are elevated
up to about 20 times
This seems
well correlated with a decrease in active white matter lesions detected by MRI
This clinical improvement is
however followed by temporary rebound exacerbations at post-partum, when the
hormone levels decline
a shift from Th1 to Th2 immune response, expansion of
suppressive regulatory T lymphocytes and decrease in the number of circulating
CD16+ natural killer (NK)-cells
Th2 cytokines are
associated with down-regulation of Th1 cytokines and this Th2 shift is believed
to provide protection from allograft rejection during pregnancy as well as from
Th1-mediated autoimmune disease
it is
worth noting that the levels of other hormones with anti-inflammatory activity
(1,25-dihydroxy-vitamin D3, norepinephrine, cortisol) also increase
by 2 to 4 times during late pregnancy
1,25-dihydroxy vitamin D3
induces regulatory T-cell function important for development of self-tolerance
breast-feeding does not alter the
relapse rate in women with MS
Leptin is a pleiotropic
hormone produced primarily by adipocytes but also by T lymphocytes and neurons
Several lines of evidence indicate that leptin
contributes to EAE/MS pathogenesis, influencing its onset and clinical severity,
by acting as a proinflammatory cytokine which promotes regulatory T cell (Treg)
anergy and hyporesponsiveness, resulting in increased Th1 (TNFalpha, INFgamma)
and reduced Th2 (IL-4) cytokine production
circulating leptin levels are increased in relapsing-remitting MS
patients (men and women analyzed together) while the
CD4+CD25+Treg population decreases
As the leptin plasma concentrations are
proportional to the amount of fat tissue, obese/overweight individuals produce
higher levels of leptin
Nielsen et al found that estradiol and progesterone exert
neuroprotection against glutamate neurotoxicity, while MPA antagonizes the
neuroprotective effect of estradiol and exacerbated neuron death induced by
glutamate excitotoxicity