inFlammatorY cascaDe
The first chemical released during the inflammatory cascade which activates
the immune system is histamine. Histamine release is activated by bacterial
toxins, heat, UV radiation, trauma, and proteolytic enzymes from invading cells,
damaged cells or allergens. Then prostaglandins, leukotrienes, and then cytokines
are released to activate the white blood cells—macrophages and basophils, which
produce free radicals during their attack. Histamine stimulates prostaglandin release
which increases vascular permeability. Then leukotrienes further increase vascular
permeability promoting swelling (edema) caused by the local accumulation of fluids,
this creates pain and restricted mobility due to the swelling. The inflammatory
cascade is mediated by proinflammatory cytokines which are macrophage-derived,
immunoregulatory peptides that target organ receptors in response to injury
or infection. Cytokines complete the inflammatory process by bringing active
leukocytes to the injury site.
After proinflammation, during the healing and repair phase, first cortisol is
released to stop the production of proinflammatory “bad” eicosanoids; however
cortisol also shuts down the “’good” eicosanoids. Glucocorticoids are considered
as key modulators of glycogen homeostasis in peripheral tissues. Cortisol
stimulates several processes that collectively serve to increase and maintain normal
concentrations of glucose in blood. Cortisol also increases insulin resistance,
impairs immunity and damages neurons in the hippocampus (learning, memory).
The macrophages then eat up the dead cells to make way for the regeneration of
damaged tissue.
A high glycemic carbohydrate diet increases insulin production, which in turn
promotes increased arachidonic acid (aa). This encourages the body to store
away AA in fat deposits to keep inflammation under control. As adipose tissues
fills with AA there is an over production of pro-inflammatory eicosanoids in the
fat cells, which generate systemic silent inflammation—promoting the production
of inflammatory cytokines like Tumor Necrosis Factor and Interleukin-6 and
essentially mounting an inflammatory response to infection even when there
isn’t one.
Visceral fat is found deep in the abdomen packed in between internal organs.
The more of this belly fat we have the higher our silent inflammation, which in
turn increases our insulin resistance leading to the susceptibility to type-2 diabetes.
Insulin resistance appears to be mediated by Tumor Necrosis Factor (TNF)—high
dose fish oil decreases TNF, lowering insulin resistance and insulin levels, and this
allows the fat stores to be utilized for energy rather than in generating obesity. Thus
the key point in Dr. Sears program is that to lose weight and reverse diabetes you
have to reduce your silent inflammation. In fact silent inflammation plays into
all degenerative disease; for example high blood glucose feeds cancer cells while
an excess of insulin encourages them to divide, so taking fish oil to reduce silent
inflammation and to promote the production of “good” eicosanoids is one of the
most effective means of preventing and reversing cancer.