What is Inflammation?

Inflammation is a complex biological process in which the body’s white blood cells and beneficial chemicals produced in the body provide protection from infection caused by foreign substances, such as Pathogenic (Harmful) bacteria, and yeast, viruses and some harmful chemicals. It is a innate protective attempt by the body to remove the injurious substance and to initiate the healing process for the tissue. As such, inflammation is part of the normal regenerative process. Without inflammation, wounds and infections would never heal and there would be progressive destruction of tissues. The goal is not to stop inflammation, but to restore normal amounts in the inflammatory processes.

In some conditions, however, the body’s immune system inappropriately triggers an inflammatory response when there are no foreign substances to fight off. In these autoimmune situations the body’s normally protective immune system causes damage to its own tissues. The ability of the immune system to cause too much inflammation, and actually damage perfectly good tissue instead of helping it advance the heal process; this is why the inflammation process must be tightly regulated by the body.

Again, the goal is not to stop inflammation, but to restore normal inflammatory processes. The biological processes of the immune system which maintain the normal inflammatory processes are heavily regulated by cytokines – signaling proteins and glycoproteins involved in cellular communication. 

What are the effects of Abnormal Inflammation?

The five clinical characteristic signs of inflammation are

1. redness (Latin rubor),

2. heat (calor),

3. swelling (tumor),

4. pain (dolor),

5. loss of function (functio laesa).

Excessive or chronic inflammation also results in increased biomarkers of inflammation, which are also associated with increased morbidity and mortality.

What are biomarkers?

In medicine, a biomarker can be a substance that is introduced into an organism as a means to examine organ function or other aspects of health. More specifically, a biomarker indicates a change in expression or state of a protein that correlates with the risk or progression of a disease, or with the susceptibility of the disease to a given proposed treatment.

What are the useful Biomarkers of inflammation?

This list is not all inclusive, but it will give the reader an indication of the more popular methods and the idea behind their use.

1. Increased Erythrocyte Sedimentation Rate

The erythrocyte sedimentation rate (ESR), also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells precipitate in a period of 1 hour. It is a common hematology test which is a non-specific measure of inflammation. To perform the test, anticoagulated blood is placed in an upright tube, known as a Westergren tube, and the rate at which the red blood cells fall is measured and reported in mm/h. Since the introduction of automated analyzers into the clinical laboratory, the ESR test has been automatically performed.

The ESR is governed by the balance between pro-sedimentation factors, mainly fibrinogen, and those factors resisting sedimentation, namely the negative charge of the erythrocytes (zeta potential). When an inflammatory process is present, the high proportion of fibrinogen in the blood causes red blood cells to stick to each other. The red cells form stacks called ‘rouleaux’ which settle faster. Rouleaux formation can also occur in association with some lymphoproliferative disorders in which one or more immunoglobulins are secreted in high amounts. Rouleaux formation can, however, be a normal physiological finding in horses, cats and pigs.

The ESR is increased by any cause or focus of inflammation. The ESR is increased in pregnancy or rheumatoid arthritis, and decreased in polycythemia, sickle cell anemia, hereditary spherocytosis, and congestive heart failure. The basal ESR is slightly higher in females

2. Increased C – reactive protein

C-reactive protein (CRP) is a protein found in the blood, the levels of which rise in response to inflammation (an acute-phase protein). Its physiological role is to bind to phosphocholine expressed on the surface of dead or dying cells (and some types of bacteria) in order to activate the complement system via the C1Q complex.

CRP is synthesized by the liver in response to factors released by fat cells (adipocytes). It is a member of the pentraxin family of proteins. It is not related to C-peptide or protein C.

3. Increases Circulating Immune Complexes

An immune complex is formed from the integral binding of an antibody to a soluble antigen. The bound antigen acting as a specific epitope, bound to an antibody is referred to as a singular immune complex. After an antigen-antibody reaction, the immune complexes can be subject to any of a number of responses, including complement deposition, opsonization, phagocytosis, or processing by proteases.

Red blood cells carrying CR1-receptors on their surface may bind C3b-decorated immune complexes and transport them to phagocytes, mostly in liver and spleen, and return back to the general circulation. Referred to as Circulating Immune Complexes

 
4. Increase Cytokine Production with an Imbalance of Th1 & Th2 Cytokines

Cytokines (Greek cyto-, cell; and -kinos, movement) are any of a number of substances that are secreted by specific cells of the immune system which carry signals locally between cells, and thus have an effect on other cells. They are a category of signaling molecules that are used extensively in cellular communication. They are proteins, peptides, or glycoproteins. The term cytokine encompasses a large and diverse family of polypeptide regulators that are produced widely throughout the body by cells of diverse embryological origin.

Further, as molecules, cytokines are not limited to their immunomodulatory role. For instance, cytokines are also involved in several developmental processes during embryogenesis. Never the less biomarkers for cytokines have been established.

5. Abnormal Levels of Immunoglobulins (IgG, IgE, IgA, IgM)

Immunoglobulins, abbreviated Ig are gamma globulin proteins that are found in blood or other bodily fluids of vertebrates, and are used by the immune system to identify and neutralize foreign objects, such as bacteria and viruses. They are typically made of basic structural units—each with two large heavy chains and two small light chains—to form, for example, monomers with one unit, dimers with two units or pentamers with five units. Antibodies are produced by a kind of white blood cell called a plasma cell

Though the general structure of all antibodies is very similar, a small region at the tip of the protein is extremely variable, allowing millions of antibodies with slightly different tip structures, or antigen binding sites, to exist. This region is known as the hypervariable region. Each of these variants can bind to a different target, known as an antigen. This huge diversity of antibodies allows the immune system to recognize an equally wide variety of antigens. The unique part of the antigen recognized by an antibody is called the epitope. Recognition of an antigen by an antibody tags it for attack by other parts of the immune system. Antibodies can also neutralize targets directly by, for example, binding to a part of a pathogen that it needs to cause an infection. Immunoglobulin biomarker measurement use is helpful in pathogen and foreign objects causes.

6. Increased Fibrin Activation & Fibrosis

Fibrin and fibrin scaffold is a network of protein that holds together and supports a variety of living tissues, especially in response to injury. It is provided naturally by the body after injury, but also can be engineered as a tissue substitute to speed healing. The scaffold consists of naturally occurring biomaterials composed of cross-linked fibrin network and has a broad use in biomedical applications.

Fibrin consists of the blood proteins fibrinogen and thrombin which participate in blood clotting. Fibrin glue or fibrin sealant is also referred to as a fibrin based scaffold and used to control surgical bleeding, speed wound healing, seal off hollow body organs or cover holes made by standard sutures, and provide slow-release delivery of medications like antibiotics to tissues exposed.

Each biomedical application has its own characteristic requirement for different kinds of tissues and recent studies with fibrin scaffold are promising towards faster recovery, less complications and long-lasting solutions. The opposite effect is referred to as Fibrinolysis or the breaking of fibrin.

7.  Increased Amyloid Production & Deposition  

Amyloids are insoluble fibrous protein aggregates sharing specific structural traits. Abnormal accumulation of amyloid in organs may lead to amyloidosis, and may play a role in various other neurodegenerative diseases.

The name amyloid comes from the early mistaken identification of the substance as starch (amylum in Latin), based on crude iodine-staining techniques. For a period, the scientific community debated whether or not amyloid deposits were fatty deposits or carbohydrate deposits until it was finally resolved that it was neither, but rather a deposition of proteinaceous mass.

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