Inflammation

Within every living cell (muscle, tendon, lung, bone, etc.), there is a biochemical and cellular time bomb waiting to go off—inflammation. However, it is to be noted that inflammation is a double-edged sword. More animals (and probably people) die from an inflammatory disease than all other disease processes combined, yet without an adequate inflammatory response by the body’s cells, the living organism could not survive for long. The inflammatory response is necessary for fighting infection and the normal healing of damaged tissue.

Leg in ice
MATT GOINS

Inflammation is a good thing in most cases and we do not want to eliminate it. But because of its ability to "run wild" and do more harm than good, there is a need to control it.

The word inflammation literally means "a burning" and has been referred to in medical literature since the first century A.D. Based on the physical observations of his human patients, the Roman Cornelius Celsus formulated his famous "cardinal signs" of inflammation: calor, ruber, tumor, and dolor. The English translation yields the following: heat, redness, swelling, and pain, respectively. To this list, the famous human pathologist Rudolf Virchow added functio laesa (loss of function). By following the observations of these two famous figures in medicine, numerous people, including Louis Pasteur, made significant observations and research discoveries with regard to the causes and functions of inflammation within a living organism.

In the present time, there has been no decrease in the research interest regarding inflammation. Inflammation is high on the list of many modern medical scientists, with a great deal of emphasis on how to modify inflammatory responses in a beneficial way, typically with pharmaceuticals. The number of drugs that have been developed and studied for their anti-inflammatory actions is quite large, with significant efforts continuing to develop the "perfect" one. In addition, if specific parts of the inflammatory cycle could be "turned on" or enhanced, there could be a significant improvement in the protective aspects of the cycle.

One of the main reasons that the inflammatory process is vital to a living creature’s existence is that inflammation actually is closely integrated with the responses that constitute healing and repair of damaged tissue. The process of inflammation acts fundamentally as a "host defense" mechanism. Many of the events that occur in the acute stages of inflammation are aimed at mobilization of host defenses in order to neutralize the offending agent (as in the case of inflammation caused by such things as bacteria or a virus).

Of course, inflammation is not always caused by the invasion of tissue with a virus or bacteria; the "irritation" of tissue by virtually anything has the ability to incite some form of inflammatory reaction. Remember the suffix "itis" means inflammation: laminitis (inflammation within the laminae of the foot), gastritis (inflammation within the stomach), colitis (inflammation within the large colon due to salmonella, Potomac horse fever, or other causes), arthritis (inflammation within a joint), synovitis (inflammation of the tissue surrounding the joint), pleuritis (inflammation within the chest cavity), sinusitis (inflammation within the sinus cavities), tendonitis (inflammation within a tendon, usually from trauma). The list goes on and on.

The causes of inflammation usually are due to infection by a bacteria, virus, fungus, or parasite, or due to some mechanical trauma leading to damage of a body tissue. An allergic reaction can provoke inflammation as well.

Inflammation is an extremely complicated subject, as noted by taking up nearly 100 pages of text in a prominent veterinary pathology textbook. It is a process involving multiple participants, which means that there are many "players" within the body that get involved. Most of the action with inflammation occurs in the extremely fine blood vessels within the area of occurrence. Virtually all of the white blood cells (neutrophils, lymphocytes, eosinophils, basophils, and monocytes), as well as the blood clotting platelets and a tissue cell called the mast cell, are involved in the inflammatory response.

In response to a stimulus (infection or mechanical damage), the fine blood vessels become "leaky" and the white blood cells migrate out of the blood vessel and into the affected tissue. It is generally a "defensive" response and is the start of what needs to happen to "heal" the damaged tissue or fight off an invading organism.

The cells involved either contain or can produce more than 100 chemical mediators of the inflammatory response. These chemicals can effectively "kill" invading bacteria or parasites, neutralize invading virus particles, and regulate the entire inflammatory response. Some of them attract more cells to the area, while others further dilate the blood vessels so the new recruits can migrate into the affected area.

The chemical "histamine" is produced by the mast cell and is a prominent player in many types of inflammation, including allergy. The antihistamine drugs that many of us depend on during an allergy season are acting effectively as anti-inflammatories by reducing the production of histamine. Other chemicals of a more sinister nature are very caustic with their main purpose to kill the invader. However, if the reaction is intense, there can be a "spill over" of such chemicals, which damage the tissue in the area as well.

One of the important generalities regarding inflammation is that inflammation can be more harmful than the initiating stimulus (trauma or an invading organism). A system of such magnitude with so many constituent players can be difficult to control, but remember that the inflammatory response is a defensive one and is a "necessary evil" to start the healing process. In addition to killing invading organisms, some of the white blood cells act to ingest and "clean up" the damaged tissue in the area while reparative cells start their work. This is one way some of the cells actually kill invading microorganisms—they engulf them and once inside the cell, the invaders are killed when toxic chemicals are released around them.

The first step in the treatment of inflammation is to identify the underlying cause and work on eliminating it, if possible. In the case of bacterial infection, antibiotics might be used to augment the body’s own immune system in an effort to help eliminate the infection. You should rely upon your veterinarian to make an accurate diagnosis and, depending on which of the thousands of causes your individual horse has, offer an appropriate course of action.

Remember that inflammation (in many cases) is a good thing and we do not want to eliminate it, but because of its ability to "run wild" and do more harm than good, there is a need to control it. In some diseases, such as laminitis, where almost all of the damage is caused by the inflammatory process itself, it would be nice to be able to shut inflammation down completely. Unfortunately, the drugs and other therapies to do that don’t exist—yet. In most cases, with the horse, an anti-inflammatory is used as some method of pain control.

The steroid and non-steroidal anti-inflammatory drugs (NSAIDs, both of which will be discussed next month in this column) work in one very specific area within the biochemistry of inflammation. This area represents only a portion of the activities causing the inflammatory process. That means the drugs can help to control inflammation, but they cannot shut it down completely. Steroids have a greater effect, but can slow down the healing process, so they must be used carefully.

The prostaglandins are a major group of chemicals produced at a site of inflammation. It is the goal of most of the anti-inflammatory drugs to reduce the production of the prostaglandins. When a cell is damaged, it releases a chemical called arachidonic acid from its membrane. That chemical subsequently is converted into the prostaglandins and some other inflammatory chemicals called HETEs and leukotrienes. A steroid anti-inflammatory (i.e., Azium) blocks the release of arachidonic acid and, therefore, reduces the production of all of the subsequent inflammatory chemicals. The non-steroidal anti-inflammatory drugs block the enzymes that convert the arachidonic acid into the prostaglandins, but do not affect the production of other chemicals.

At that point, it is important to point out that of the numerous prostaglandins, not all of them are bad. Prostaglandin "E" plays a very important protective role within the gastrointestinal system and kidney, such that a decrease in its production can predispose a horse to the development of ulcers within the stomach and colon, and possibly kidney problems. That is why there is a potential toxicity of most of the currently available non-steroidal anti-inflammatory drugs (and steroids). There is great interest by pharmaceutical companies in the development of a more specific non-steroidal drug that will reduce the production of the bad prostaglandins and leave the good ones alone.

About the Author

Michael Ball, DVM

Michael A. Ball, DVM, completed an internship in medicine and surgery and an internship in anesthesia at the University of Georgia in 1994, a residency in internal medicine, and graduate work in pharmacology at Cornell University in 1997, and was on staff at Cornell before starting Early Winter Equine Medicine & Surgery located in Ithaca, N.Y. He is also an FEI veterinarian and works internationally with the United States Equestrian Team.

Ball authored Understanding The Equine Eye, Understanding Basic Horse Care, and Understanding Equine First Aid, published by Eclipse Press and available at www.exclusivelyequine.com or by calling 800/582-5604.

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