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Inflammation

Response to infection, antibody-antigen reactions, mechanical irritation or injury.

A set of biologic mechanisms to constrain and neutralize infectious and other injurious agents that enter the body.

Inflammation occurs  naturally.

Manifestations of inflammation include fever, alterations in leukocyte counts, cardiovascular reactions, endocrine responses, and reorientation of metabolism in association with increased production of molecules referred to as acute-phase proteins.

Inflammation protects against toxins, infection, and injury, but when it happens too often it can trigger diseases.

Inflammation involves biologic mechanisms that contain invasive pathogens and resolve injuries by activating innate and adaptive immune responses.

The immune system recognizes foreign invaders, responds proportionally to the pathologic burden, and then returns to homeostasis.

Response is release of proinflammatory cytokines which mediate a systemic reaction.

The inflammatory response requires a balance between sufficient cytokine production to eliminate the pathogen but to avoid hyperinflammatory responses which can cause clinically significant collateral damage.

Complex interaction between various soluble factors and inflammatory cells.

Serves as a host surveillance system to limit injury.

It is mediated by molecular sensors on membranes of host defense cells, in cellular cytoplasm, or in extracellular fluid.

Activation of molecular sensors generate mediators that give rise to detectable manifestations of inflammation.

Inflammation plays an essential role in aging and age-related diseases. 

Inflammation may develop as a result of immune dysregulation in autoimmune or malignant disorders.

Cytokines including tumor necrosis factor, interleukin-1, interleukin-6, and interferon-gamma, are produced by inflammatory cells within the first hours after the onset of inflammation.

Cytokines restrict erythropoiesis directly and indirectly, and shorten the red blood cell lifespan.

Starts an acute phase reaction with an increase in a common set of plasma proteins referred to as acute phase proteins (APPs) which are predominantly synthesized in the liver and they are essential to reestablish systemic homeostasis in response to infection.

Involves complex reaction to various insults of vascular tissue with influx of leucocytes, connective tissue cells, fibrous proteins, such as collagen or elastin, and glycoproteins, fibronectin, laminin and proteoglycans.

Initiation of inflammatory response involves increased blood flow by capillary dilation, escape of plasma proteins from the bloodstream and extravasation and accumulation of neutrophils at the site of injury.

Patients with systemic inflammatory conditions have higher rates of cardiovascular disease.

Systemic inflammation is involved in the pathogenesis of atherosclerosis and is measured by high sensitivity C reactive proteins, a marker for future risk of cardiovascular disease.

Inflammation accelerates atherosclerosis.

Likely accelerates development of diabetes mellitus.

Inflammation may cause insulin resistance.

Rheumatoid arthritis and psoriasis, two systemic inflammatory diseases predispose to insulin resistance and may increase risk of diabetes.

Inflammatory cells are participants in the neoplastic process, promoting proliferation, survival and migration in the tumor and microenvironment.

Systemic inflammation elevates the C reactive protein and changes the proportion of white blood cells, increasing the neutrophil count and decreasing the lymphocyte count.

TNF and IL-6 block function of insulin at the receptor level, and CRP and plasminogen activator inhibito-1 are negatively associated with insulin sensitivity.

Chronic inflammation associated with an increased risk of cancer.

Chronic low-grade inflammation is associated with metabolic liver disease, and colon neoplasia.

Hypothesized that chronic inflammation results in excessive cell proliferation and activation of cellular actions that can lead to DNA damage, and persistent irritation and inflammation can subsequently promote initiated cells to tumor growth.

A family of signaling receptors, Toll-like receptors (TLRs,) drive inflammatory events.

May develop into chronic inflammation from acute inflammation or may develop insidiously without acute symptoms.

Chronic inflammation marked by predominance of macrophages and lymphocytes along with proliferation of small blood vessels, fibrosis and necrosis.

Besides making one feel achy and lethargic, chronic inflammation is associated with a range of chronic diseases including cancer, diabetes, and cardiovascular disease.  

 

Chronic inflammation linked to:

Cancer

Heart disease 

Diabetes

Alzheimer’s disease

Depression 

Microbes activate complement and toll-like receptors releasing mediators effecting vasculature.

Contributes to all phases of atherosclerosis, from fatty streaking to cardiovascular disease.

Acute inflammation is a short duration and is characterized by vascular and cellular alterations.

In acute inflammation cells and molecules of the immune system enter the affected site.

The process of movement of fluids proteins,white blood cells, particularly neutrophils, into the interstitial tissue is referred to as exudate.

In acute inflammation activation of compliment generates C3b which coats the surface of the pathogen.

In acute inflammation neutrophil chemoattractant and activated C5a is also produced and with C3a and C4a trigger the release of histamine by granulating mast cells.

The exudate that occurs with acute inflammation causes contraction of smooth muscles and increases vascular permeability.

The pathogen and damaged tissues up regulate the expression of adhesion molecules on the vascular endothelium.

Patients with depression have increases in inflammatory cytokines in the blood and cerebral spinal fluid.

Patients who have treatment resistant depression tend to have an increase in inflammatory markers.

Inflammation coming from an infectious source or from an autoimmune disease is a risk factor for schizophrenia, not only during development but also later in life.

Obese men have increased levels of inflammatory markers in their seminal fluid and lower sperm quality, both of which correlate with their body mass index (BMI):suggesting that chronic inflammation in male reproductive organs explains the link between obesity and reduced fertility.

Adipose tissue in the epicardium is normally a source of cardiovascular development, regeneration, and nourishment, but when activated by systemic inflammation it becomes a source of pro inflammatory adipocytokines including leptin, tumor necrosis  factor, Interleukin 1-beta and interleukin-6 which are transmitted directly to underlying tissues.
 
Systemic inflammation leads to epicardial adipose tissue expansion and explains atrial and ventricular myopathies.
The triad of accelerated coronary atherosclerosis leading to myocardial infarction, atrial myopathy leading to atrial fibrillation and from thromboembolic stroke, and ventricular myopathy leading to heart failure with preserved ejection fraction is seen in many chronic systemic inflammatory disorders including rheumatoid arthritis, chronic HIV infection, non-alcoholic steatohepatitis, and chronic kidney disease: epicardial adipose tissue inflammatory triad
 
Long-standing systemic inflammatory state can activate visceral fat depots, and the most relevant adipose tissue is that residing in the epicardium.
Inflammatory biomarkers commonly preceded the onset of atrial fibrillation and heart failure with preserved ejection fraction in the general community.

Canakinumab an Il-1 beta inhibitor (CANTOS atrial), reduced inflammatory associated diseases such as cardio metabolic inflammation like diabetes, stroke, and chronic kidney disease and in patients with lung cancer.

Inflammation can be assessed via calprotectin or lactoferrin assays.

Fecal calprotectin and lactoferrin are antimicrobial peptides released by activated neutrophils, and neutrophils are the defining feature of acute inflammation.

Elevated calprotectin or lactoferrin in stools are highly sensitive and specific for intestinal inflammation from any cause: includes active colitis in inflammatory bowel disease and immune checkpoint inhibitor induced colitis.

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