Inflammation

Inflammation (Latin, inflammare, to set on fire) is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process. Inflammation is not a synonym for infection, even in cases where inflammation is caused by infection. Although infection is caused by a microorganism, inflammation is one of the responses of the organism to the pathogen.

Without inflammation, wounds and infections would never heal. Similarly, progressive destruction of the tissue would compromise the survival of the organism. However, chronic inflammation can also lead to a host of diseases, such as hay fever, atherosclerosis, rheumatoid arthritis, and even cancer (e.g., gallbladder carcinoma). It is for that reason that inflammation is normally closely regulated by the body.

Inflammation can be classified as either acute or chronic. Acute inflammation is the initial response of the body to harmful stimuli and is achieved by the increased movement of plasma and leukocytes (especially granulocytes ) from the blood into the injured tissues. A cascade of biochemical events propagates and matures the inflammatory response, involving the local vascular system, the immune system, and various cells within the injured tissue. Prolonged inflammation, known as chronic inflammation, leads to a progressive shift in the type of cells present at the site of inflammation and is characterized by simultaneous destruction and healing of the tissue from the inflammatory process.

Types

There are two basic types of inflammation – acute and chronic. Acute inflammation is of short duration, which could be anything from a few minutes to a few days. Such inflammation is caused by foreign substances entering the body, or by physical damage. A viral infection may also precipitate acute inflammation. Chronic inflammation, on the other hand, is long lasting. It may persist for weeks, months or even years. Chronic inflammation may be brought on by acute inflammation or it may be the result of an auto immune disease.

Two other, less common types of inflammation are sub-acute inflammation and granulomatous chronic inflammation. Sub-acute inflammation has clinical features of both acute and chronic inflammation – it is an intermediary stage between the two. Granulomatous chronic inflammation is a special type of chronic inflammation that is associated with tuberculosis and some lesser known diseases.

Cardinal signs

1. Redness
2. Swelling
3. Heat
4. Pain
5. Loss of function

Process of acute inflammation

The process of acute inflammation is initiated by cells already present in all tissues, mainly resident macrophages, dendritic cells, histiocytes, Kupffer cells and mastocytes. At the onset of an infection, burn, or other injuries, these cells undergo activation and release inflammatory mediators responsible for the clinical signs of inflammation. Vasodilation and its resulting increased blood flow causes the redness (rubor) and increased heat (calor). Increased permeability of the blood vessels results in an exudation (leakage) of plasma proteins and fluid into the tissue (edema), which manifests itself as swelling (tumor). Some of the released mediators such as bradykinin increase the sensitivity to pain (hyperalgesia, dolor). The mediator molecules also alter the blood vessels to permit the migration of leukocytes, mainly neutrophils, outside of the blood vessels (extravasation) into the tissue. The neutrophils migrate along a chemotactic gradient created by the local cells to reach the site of injury. The loss of function (functio laesa) is probably the result of a neurological reflex in response to pain.

In addition to cell-derived mediators, several acellular biochemical cascade systems consisting of preformed plasma proteins act in parallel to initiate and propagate the inflammatory response. These include the complement system activated by bacteria, and the coagulation and fibrinolysis systems activated by necrosis, e.g. a burn or a trauma.

The acute inflammatory response requires constant stimulation to be sustained. Inflammatory mediators have short half lives and are quickly degraded in the tissue. Hence, acute inflammation ceases once the stimulus has been removed. 

The symptoms of inflammation include:

• Redness
• Swollen joint that's tender and warm to the touch
• Joint pain
• Joint stiffness
• Loss of joint function

Often, only a few of these symptoms are present.

Inflammation may also be associated with general "flu"-like symptoms including:

• Fever
• Chills
• Fatigue/loss of energy
• Headaches
• Loss of appetite
• Muscle stiffness

Inflammatory disorders

Abnormalities associated with inflammation comprise a large, officially unrelated group of disorders which underlie a vast variety of human diseases. The immune system is often involved with inflammatory disorders, demonstrated in both allergic reactions and some myopathies, with many immune system disorders resulting in abnormal inflammation. Non-immune diseases with etiological origins in inflammatory processes are thought to include cancer, atherosclerosis, and ischaemic heart disease.

A large variety of proteins are involved in inflammation, and any one of them is open to a genetic mutation which impairs or otherwise dysregulates the normal function and expression of that protein.

Examples of disorders associated with inflammation include:

• Acne vulgaris
• Asthma
• Autoimmune diseases
• Chronic prostatitis
• Glomerulonephritis
• Hypersensitivities
• Inflammatory bowel diseases
• Pelvic inflammatory disease
• Reperfusion injury
• Rheumatoid arthritis
• Sarcoidosis
• Transplant rejection
• Vasculitis
• Interstitial cystitis

Resolution of inflammation

The inflammatory response must be actively terminated when no longer needed to prevent unnecessary "bystander" damage to tissues. Failure to do so results in chronic inflammation, and cellular destruction. Resolution of inflammation occurs by different mechanisms in different tissues. Mechanisms which serve to terminate inflammation include:

• Short half-life of inflammatory mediators in vivo.
• Production and release of Transforming growth factor (TGF) beta from macrophages
• Production and release of Interleukin 10 (IL-10)
• Production of anti-inflammatory lipoxins
• Downregulation of pro-inflammatory molecules, such as leukotrienes
• Upregulation of anti-inflammatory molecules such as the Interleukin 1 receptor antagonist or the soluble tumor necrosis factor receptor (TNFR)
• Apoptosis of pro-inflammatory cells
• Desensitization of receptors
• Increased survival of cells in regions of inflammation due to their interaction with the extracellular matrix (ECM)
• Downregulation of receptor activity by high concentrations of ligands
• Cleavage of chemokines by matrix metalloproteinases (MMPs) might lead to production of anti-inflammatory factors. 

How Are Inflammatory Diseases Diagnosed?

Diagnosis of inflammatory diseases consists of all or some of the following:

• Complete medical history and physical exam.
• The location of painful joints.
• Presence of joint stiffness in the morning.
• Evaluation of other symptoms.
• Results of X-rays, blood tests, and other studies.

Can Inflammation Affect Internal Organs?

Yes. Inflammation can affect organs as part of an autoimmune disorder. The type of symptoms depends on which organs are affected. For example:

• Inflammation of the heart (myocarditis) may cause vague chest pain or fluid retention.
• Inflammation of the small tubes that transport air to the lungs (bronchiolitis) may cause shortness of breath.
• Inflammation of the kidneys (nephritis) may cause high blood pressure or kidney failure.
• Inflammation of the eye (iritis or uveitis) may cause pain or decreased vision.
• Inflammation of the muscles (polymyositis) may cause achiness or weakness.
• Inflammation of the blood vessels (vasculitis) may cause rash, headaches, or internal organ damage.

Pain may not be a main symptom since many organs do not have pain-sensitive nerves. Treatment of organ inflammation is directed at the cause of inflammation whenever possible.

Outcomes

The outcome in a particular circumstance will be determined by the tissue in which the injury has occurred and the injurious agent that is causing it. Here are the possible outcomes to inflammation:

1. Resolution
   The complete restoration of the inflamed tissue back to a normal status. Inflammatory measures such as vasodilation, chemical production, and leukocyte infiltration cease, and damaged parenchymal cells regenerate. In situations where limited or short lived inflammation has occurred this is usually the outcome.
2. Fibrosis
   Large amounts of tissue destruction, or damage in tissues unable to regenerate, can not be regenerated completely by the body. Fibrous scarring occurs in these areas of damage, forming a scar composed primarily of collagen. The scar will not contain any specialized structures, such as parenchymal cells, hence functional impairment may occur.
3. Abscess Formation
   A cavity is formed containing pus, an opaque liquid containing dead white blood cells and bacteria with general debris from destroyed cells.
4. Chronic inflammation
   In acute inflammation, if the injurious agent persists then chronic inflammation will ensue. This process, marked by inflammation lasting many days, months or even years, may lead to the formation of a chronic wound. Chronic inflammation is characterised by the dominating presence of macrophages in the injured tissue. These cells are powerful defensive agents of the body, but the toxins they release (including reactive oxygen species) are injurious to the organism's own tissues as well as invading agents. Consequently, chronic inflammation is almost always accompanied by tissue destruction.

What Drugs Are Used to Treat Inflammatory Diseases?

There are many drugs available to decrease joint pain, swelling, and inflammation and hopefully prevent or minimize the progression of the inflammatory disease. These medications include:

• Anti-inflammatory pain reliever drugs (NSAIDs -- such as aspirin, ibuprofen, or Celebrex).
• Corticosteroids (such as prednisone).
• Other medications* include chemotherapy drugs, disease modifying treatments, biologic therapy, or narcotic pain relievers.

*Some of these medications are traditionally used to treat other conditions such as cancer and inflammatory bowel disease or to prevent organ rejection after transplants. However, when "chemotherapy" types of medications are used to treat inflammatory diseases, the doses are significantly lower and the risks of side effects tend to be considerably less than when prescribed in higher doses for cancer.

When you are prescribed any drug, it is important to meet with your doctor regularly so he or she can check its effectiveness and detect the development of any side effects.