What Is Inflammation? What Causes Inflammation?

Inflammation is the body's attempt at self-protection; the aim being to remove harmful stimuli, including damaged cells, irritants, or pathogens - and begin the healing process.

When something harmful or irritating affects a part of our body, there is a biological response to try to remove it, the signs and symptoms of inflammation, specifically acute inflammation, show that the body is trying to heal itself. Inflammation does not mean infection, even when an infection causes inflammation. Infection is caused by a bacterium, virus or fungus, while inflammation is the body's response to it.

The word inflammation comes from the Latin "inflammo", meaning "I set alight, I ignite".

Inflammation is part of the body's immune response. Initially, it is beneficial when, for example, your knee sustains a blow and tissues need care and protection. However, sometimes inflammation can cause further inflammation; it can become self-perpetuating. More inflammation is created in response to the existing inflammation.

According to Medilexicon's medical dictionary, Inflammation is:

"A fundamental pathologic process consisting of a dynamic complex of histologically apparent cytologic changes, cellular infiltration, and mediator release that occurs in the affected blood vessels and adjacent tissues in response to an injury or abnormal stimulation caused by a physical, chemical, or biologic agent, including the local reactions and resulting morphologic changes; the destruction or removal of the injurious material; and the responses that lead to repair and healing.

The so-called cardinal signs of inflammation are rubor, redness; calor, heat (or warmth); tumor, swelling; and dolor, pain; a fifth sign, functio laesa, inhibited or lost function, is sometimes added. All these signs may be observed in certain instances, but none is necessarily always present."

Plaque in coronary artery disease linked to inflammation - scientists from Stanford University, California, linked 25 new genetic regions to coronary artery disease. They found that people with coronary artery disease, the leading cause of death globally, are most likely predisposed to the disease because they have gene variants linked to inflammation.

Inflammation helps wounds heal

Our immediate reaction to a swelling is to try to bring it down. Bearing in mind that inflammation is an essential part of the body's attempt to heal itself, patients and doctors need to be sure that the treatments to reduce swelling are absolutely necessary and to not undermine or slow down the healing process.

The first stage of inflammation is often called irritation, which then becomes inflammation - the immediate healing process. Inflammation is followed by suppuration (discharging of pus). Then there is the granulation stage, the formation in wounds of tiny, rounded masses of tissue during healing. Inflammation is part of a complex biological response to harmful stimuli. Without inflammation, infections and wounds would never heal.

Neuroscientists at the Lerner Research Institute at the Cleveland Clinic in Ohio found that inflammation actually helps to heal damaged muscle tissue. Their findings clash with how sportspeople with inflammation are treated - health professionals always try to control the inflammation to encourage healing. The researchers say their findings may lead to new therapies for acute muscle injuries caused by freeze damage, medications, chemicals and trauma.

Lan Zhou, M.D., Ph.D., said that patients should be very closely monitored when therapies to combat inflammation are used to make sure that the benefits of inflammation are not completely eliminated.

Inflammation is part of our innate immunity

Our innate immunity is what is naturally present in our bodies when we are born, and not the adaptive immunity we get after an infection or vaccination. Innate immunity is generally non-specific, while adaptive immunity is specific to one pathogen:

Whooping cough vaccine - example of immunity being specific to one pathogen

After being vaccinated for whooping cough (pertussis), we develop immunity to Bordetella pertussis or Bordetella parapertussis, types of bacteria that cause pertussis. This is an example of adaptive immunity - the immunity was not there before receiving the vaccine.

Inflammation is seen as a mechanism of innate immunity.

What is the difference between chronic inflammation and acute inflammation?

Acute inflammation - starts rapidly (rapid onset) and quickly becomes severe. Signs and symptoms are only present for a few days, but in some cases may persist for a few weeks.

Examples of diseases, conditions, and situations which can result in acute inflammation include: acute bronchitis, infected ingrown toenail, sore throat from a cold or flu, a scratch/cut on the skin, exercise (especially intense training), acute appendicitis, acute dermatitis, acute tonsillitis, acute infective meningitis, acute sinusitis, or a blow.

Chronic inflammation - this means long-term inflammation, which can last for several months and even years. It can result from:

• Failure to eliminate whatever was causing an acute inflammation
• An autoimmune response to a self antigen - the immune system attacks healthy tissue, mistaking it (them) for harmful pathogens.
• A chronic irritant of low intensity that persists

Examples of diseases and conditions with chronic inflammation include: asthma, chronic peptic ulcer, tuberculosis, rheumatoid arthritis, chronic periodontitis, ulcerative colitis and Crohn's disease, chronic sinusitis, and chronic active hepatitis (there are many more).

Our infections, wounds and any damage to tissue would never health without inflammation - tissue would become more and more damaged and the body, or any organism, would eventually perish.

However, chronic inflammation can eventually cause several diseases and conditions, including some cancers, rheumatoid arthritis, atherosclerosis, periodontitis, and hay fever. Inflammation needs to be well regulated.

What happens during acute inflammation?

Within a few seconds or minutes after tissue is injured, acute inflammation starts to occur. The damage may be a physical one, or might be caused by an immune response.

Three main processes occur before and during acute inflammation:

• Arterioles, small branches of arteries that lead to capillaries that supply blood to the damaged region dilate, resulting in increased blood flow


• The capillaries become more permeable, so fluid and blood proteins can move into interstitial spaces (spaces between tissues).


• Neutrophils, and possibly some macrophages migrate out of the capillaries and venules (small veins that go from a capillary to a vein) and move into interstitial spaces. A neutrophil is a type of granulocyte (white blood cell), it is filled with tiny sacs which contain enzymes that digest microorganisms. Macrophages are also a type of white blood cells that ingests foreign material.
  
  Klaus Ley, M.D., a scientist at the La Jolla Institute for Allergy & Immunology, reported in a study published in Nature that neutrophils are the human body's first line of defense; they are the main cells that protect us from bacterial infections. Their protective function is a positive one, however, they also have inflammatory properties that may eventually lead to heart disease and several autoimmune diseases, such as lupus. Effectively manipulating neutrophils is vital in disrupting inflammatory diseases.

When our skin is scratched (and the skin is not broken), one may see a pale red line. Soon the area around that scratch goes red, this is because the arterioles have dilated and the capillaries have filled up with blood and become more permeable, allowing fluid and blood proteins to move into the space between tissues.

Edema - the area then swells as further fluid builds up in the interstitial spaces.

The five cardinal signs of acute inflammation - "PRISH"

An ingrown toenail with the five PRISH signs; pain, redness, immobility, swelling and heat



• Pain - the inflamed area is likely to be painful, especially when touched. Chemicals that stimulate nerve endings are released, making the area much more sensitive.
• Redness - this is because the capillaries are filled up with more blood than usual
• Immobility - there may be some loss of function
• Swelling - caused by an accumulation of fluid
• Heat - as with the reason for the redness, more blood in the affected area makes it feel hot to the touch

The five classical signs of inflammation

Although Latin terms are still used widely in Western medicine, local language terms, such as English, are taking over. PRISH is a more modern acronym which refers to the signs of inflammation. The traditional Latin based terms have been around for two thousand years:

• Dolor - Latin term for "pain"
• Calor - Latin term for "heat"
• Rubor - which in Latin means "redness"
• Tumor - a Latin term for "swelling"
• Functio laesa - which in Latin means "injured function", which can also mean loss of function

Dolor, Calor, Rubor, and Tumor were first described and documented by Aulus Cornelius Celsus (ca 25 BC-ca 50), a Roman encyclopaedist. Celcius is famous for creating De Medicina, which is thought to be the only surviving section of a vast encyclopedia. De Medicina was the main source of medical reference in the Roman world for pharmacy, surgery, diet and some other medical fields.

Functio laesa - it is not clear who first described and documented the fifth sign. The majority of attributions have gone to Thomas Sydenham (1624-1689) an English physician and Rudolph Carl Virchow (1821-1902), a German doctor, biologist, politician and pathologist. Virchow is seen as one of the founders of social medicine.

These five acute inflammation signs are only relevant when the affected area is on or very close to the skin. When inflammation occurs deep inside the body, such as an internal organ, only some of the signs may be detectable. Some internal organs may not have sensory nerve endings nearby, so there is be no pain, as is the case with some types of pneumonia (acute inflammation of the lung). If the inflammation from pneumonia pushes against the parietal pleura (inner lining of the surface of the chest wall), then there is pain.

Acute and chronic inflammation compared

The lists below show the difference between chronic and acute inflammation regarding the causative agents, which major cells are involved, features regarding onset, duration, and outcomes:

Acute Inflammation

• Causative agents - harmful bacteria or injury to tissue
• Major cells involved - mainly neutrophils, basophils (in the inflammatory response), and eosinophils (response to parasites and worms), and mononuclear cells (macrophages, monocytes)
• Primary mediators - eicosanoids, vasoactive amines
• Onset (when does the inflammation start) - straight away
• Duration - short-lived, only a few days
• Outcomes - the inflammation either gets better (resolution), develops into an abscess, or becomes a chronic inflammation

Chronic inflammation

• Causative agent - non-degradable pathogens that cause persistent inflammation, infection with some types of viruses, persistent foreign bodies, overactive immune system reactions
• Major cells involved - Macrophages, lymphocytes, plasma cells (these three are mononuclear cells), and fibroblasts
• Primary mediators - reactive oxygen species, hydrolytic enzymes, IFN-γ and other cytokines, growth factors
• Duration - from several months to years
• Outcomes - the destruction of tissue, thickening and scarring of connective tissue (fibrosis), death of cells or tissues (necrosis)

Sleep quality and duration impacts on inflammation risk

Scientists at Emory University School of Medicine in Atlanta, Georgia, found in a study that sleep deprivation or poor sleep quality raise inflammation, which in turn increase the risk of developing heart disease and stroke.

The team gathered data on 525 middle-aged volunteers who had completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire, which asked detailed questions about sleep quality and duration.

They tested the participants' levels of various inflammatory markers, and then tried to see whether they could link them to quality and duration of sleep. The authors concluded:

"The researchers concluded that: "Poor sleep quality, and short sleep durations are associated with higher levels of inflammation."