Sunday, November 23, 2008



(due for publication in AFAA's American Fitness)

For those of you who have sprained your ankle and witnessed the associated swelling, warmth and pain will refer to the process as inflammation. But does the general public or the fitness instructors actually have a thorough understanding of this disease process? Inflammation is a very common part of our lexicon, we read about it in journals and articles and hear it mentioned on television. To give the reader more than a perfunctory introduction to the topic, this article will focus on the pathophysiology, define acute versus chronic inflammation, and identify those end organs that are harmed from chronic inflammation. Finally a mention of prescription medications used in the treatment of inflammation and some natural ways to fight it.

Inflammation simply put is a non-specific response to cell injury. Injury may occur due to trauma, infection or auto-immune responses. This complex process involves white blood cells (WBC), blood vessels and chemical mediators. The body relies on the inflammatory process for its own protection. Inflammation actually destroys organisms such as viruses and bacteria to prevent their reproduction and propagation in our tissues. It also limits the tissue damage to a finite area and slows the spread of invading microbes. Inflammation is also responsible for clearing debris and making way for the repair of injured tissues and organs. There are two major aspects to inflammation, cellular and vascular. The cellular component involves immune cells called neutrophils and monocytes which are responsible for “eating up” the bad guys (viruses, bacteria, etc.) by a process called phagocytosis. These cells are jointly referred to as phagocytes and will in the case of acute injury or insult migrate and adhere to vessel walls at the site of injury (a process called margination). Marginated cells will go through the vessel walls to the exact location of the injury or diseased tissue in a process called emigration. This can take six to 24 hours in the case of neutrophils and 24 – 48 hours in the case of monocytes. This accounts for the delay we see after an acute insult in the inflammation process. The vascular component is responsible for the vasodilatation, increase in blood flow and increased capillary permeability at the site of injury.

Yet another component of inflammation is the complement system or which plasma proteins are produced by our bodies to attract WBCs and degranulate mast cells. They are known as C-3, C-5, kinins (as in bradykinin and prostaglandin E). These chemical mediators are known for causing pain at the site of injury, responsible for the swelling of the diseased tissue. Plasma proteins in the aracodonic acid category produce leukotrienes which maintain inflammation (PGD2, E2, F2, Thromboxane A2). Non-steroidal Anti-inflammatory Drugs (NSAID) and steroids (cortisone) block the thromboxanes and aracodonic acid pathways to help alleviate inflammation. That is why aspirin or Motrin® is routinely prescribed when an acute insult occurs.

Other chemical mediators are interferon (alfa, beta and gamma) and tumor necrosis factor (TNF). These chemical mediators are also partly responsible for causing fever amongst other things. Fever is one of the body’s mechanisms for dealing with viral and bacterial invasion. These chemical mediators are known to respond to NSAIDs, and for this reason they are useful in combating fevers.

The result of inflammation is leukocytosis (an elevated blood WBC count), loss of appetite, fever, increase in our deep sleep time, weight loss and weakness. With the resolution of inflammation we see a return to normal vascular permeability, lessening of edema or swelling of the tissues as plasma proteins are removed by the lymphatic system and the removal of damaged cellular debris by macrophage phagocytosis.

Chronic inflammation while sharing some of the molecular components is a bit of a different animal. By definition chronic inflammation lasts for more than 2 weeks, occurs when the invading organism is not totally destroyed, a foreign body or ongoing irritant is still present, auto-immune response continues, and/or there is a very significant amount of tissue destruction. While the mechanisms of acute inflammation are well known, the pathways of chronic inflammation with their molecular pathways, propagating mechanisms and resultant disorders are far less known and understood. It is known however that chronic inflammatory conditions are a result of an overzealous immune system that continues to attack our body once its work is done on diseased tissues from an acute insult.

Chronic inflammation has an impact on almost every organ system in the human body, from our skin to the alimentary (gastrointestinal) tract, from our hearts and lungs to our brains, joints and vascular system. Examples better known to the public are rheumatoid arthritis with our joints, periodontal disease of our gums, asthma of the lungs and Crohn’s disease of our intestines. However, we also see evidence of inflammation at work in other organ systems such as psoriasis of the skin, multiple sclerosis of the neurological system and coronary disease with plaque development in our heart to name a few. Cancers are another disorder that inflammation has a part to play, it is theorized that chronic inflammation prompt a malignant change in cells and conversely cancer cells perpetuate an inflammatory microenvironment.

There are links between lipid metabolism and inflammation. Studies show a correlation between chronic inflammation and atherosclerosis (hardening of the arteries) as a pro-inflammatory state incites low-density cholesterol (LDL-C) to form plaques on artery walls. The link between periodontal disease and coronary artery disease is evident by this relationship. Poor dentition with inflammation is an independent risk factor for development of plaques on your coronary arteries. It is well documented that a sedentary lifestyle is a risk factor for chronic disease. Lack of exercise is linked to immune system dysfunction where inactivity and obesity results in a low-grade systemic inflammatory state that promotes diseases. Those individuals who do not partake in routine exercise are subject to chronic inflammation and the ravages of it on end organs. Runaway chronic inflammation is a harmful disease process that increases morbidity and mortality.

A test that has made the news lately is the high sensitivity C-reactive protein (hs-CRP) or cardiac CRP (c-CRP), they are essentially one in the same. This is a test for inflammation that correlates with cardiovascular disease (CVD). CRP is a protein produced in the liver. It is in the pentraxin family of proteins and was discovered in 1930 by Drs. Tillert and Francis as an acute phase protein of inflammation that reacted with C polysaccharide of pneumococcus in pneumonia patients thus the name C-reactive protein. The blood test throughout the years has been fine tuned and the high sensitivity CRP test is designed to assess inflammation levels that indicate risk of heart disease. For those individuals with hs-CRP of less than 1.0 mg/L they are at low risk for CVD. Those with a range of between 1.0 and 2.9 mg/L are considered at intermediate risk and those with levels greater than 3.0 mg/L are high risk for CVD.

The treatment options offered by traditional western medicine include anti-inflammatory drugs in a few different classes. Examples are NSAIDs mentioned earlier, used to treat osteo- and rheumatoid arthritis. NSAIDs are proven effective in managing pain and inflammation, but at a cost of some untoward effects on the stomach lining (resulting in ulcerative disease and gastrointestinal bleeding) and impacting the function of the kidneys (nephrotoxicity). Cortisone or corticosteroids are also used and again they have impacts on metabolism, weight gain and other hormonal axises. They are also implicated in mineral loss in our skeletal system (osteoporosis). The HMG-coA Reductase inhibitor (statin) class of drugs used to treat elevated cholesterol are reputed to have anti-inflammatory properties and are being promoted as the most important medication in the 21st century to treat cardiovascular disease, not only from the standpoint of lowering lipids, but also reducing inflammation within the coronary arteries that is responsible for plaque formation. There is even a link between inflammation and Alzheimer’s disease. Researchers have tried to persuade the medical community that statin drugs have a place in the treatment of dementia. However, in recent years it has become controversial and statins are falling out of favor as a preventive measure for Alzheimer’s disease.

It is at this point that I depart from the party line recommendations of the American College of Cardiology/ American Heart Association/National Heart, Lung and Blood Institute, and most medical society practice guidelines on the use of statin drugs. The pharmaceutical industry to the average observer is pushing hard to have statin drugs prescribed for nearly everyone in almost any situation. Physicians and medical societies are being swayed by “evidence based studies” that are in fact supported by the manufacturers of these drugs. It is my opinion that these drug companies would welcome the suggestion of placing statins in every municipal water system in the country. First, the science is biased. These studies are selected specifically by the drug companies for publications as they report the results they want. Often “negative” studies are banished from publication or hidden is some obscure journal. Secondly, these drugs are very powerful and laden with serious side effects. Only patients with severe coronary artery disease (CAD) or markedly elevated lipids or other risk factors should be prescribed these drugs and only after it is determined the benefits will outweigh the risks of these medications. In other words they should not be prescribed lightly.

The same arguments can be made for the widespread prescription of NSAIDs. The use of COX-2 inhibitors (a subclass of NSAIDs) in recent years has turned up some problems with high incidence of NSAID-induced gastrointestinal bleeding, cardiac and renal complications. Cardiac and hepatic involvement with some selective COX-2 inhibitors resulted in the FDA pulling the drugs Vioxx® and Bextra® off the market. Again the search for drugs to fight chronic inflammation is an important research priority as well as a profitable endeavor for pharmaceutical companies. The industry must proceed cautiously to find safe and effective medications and not be impetuous to turn a quick profit.

Safer and more natural ways to control chronic inflammation with fewer side effects involve the use of specific herbs. Herbs such as Arnica, Boswellia, Bromelain, Devils claw, Echinacea, Chamomile, Ginger, Turmeric, White Willow and Witch Hazel can be used as a remedy for acute and chronic inflammatory conditions. Ayurvedic and Traditional Chinese Medicine have been using them for thousands of years. Another way to protect oneself from chronic inflammation is to maintain a regular exercise routine, keeping yourself active and fit. Diet plays a major role as well, since research has shown that diets high in saturated-fats and carbohydrates are pro-inflammatory. A well balanced low-carb diet helps prevent and reduce inflammation. Not to be forgotten are the host of dietary supplements touted to reduce inflammation, too numerous to mention here, but include Vitamins A, C, D and E, along with Vitamin B-12 and the minerals copper and zinc to name a few.

Weiss, Ursula, Inflammation, Nature 454, issue 7203, 427 (24 July 2008)

Werbach, M.R., The Effects of Vitamins and Minerals on Inflammation. Townsend Letter, May 2004, #250, p.164+

(c) 2008

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