Inflammation: The Leukocyte Adhesion Cascade
Karl
Note: The image to the left is taken by infrared
technology, and shows the heat radiating from
inflammation of the back. (source)
When you have some
inflammation somewhere in your body -- the area is
usually swollen and hot. Usually also there is
pain.
If you have arthritis, you generally have inflammation. Arthritis in the hands or wrists would feel like the image to the right. You would feel heat and swelling in your wrists, and you would feel a lack of freedom in movement -- all related to inflammation.
So, we certainly think of inflammation as a "bad thing."
When you have an inflammation, what is happening inside your body? Below is a traditional explanation, with Karl Loren annotations pointing to more basic causes and actions than most doctors are willing to acknowledge.
The material quoted
below treats "inflammation" as a harmful activity, but in
the same text it acknowledges that "inflammation" is the
body's natural way of handling some invading bacteria or
other irritant. One wonders why a "natural process"
is not considered better than using a drug to actually
prevent the natural process from proceeding??
Inflammation of the bronchial tubes, through which the air you breathe passes, could close off those tubes, making it hard to breathe. Click for picture. This is the mechanical explanation of "asthma," and it would seem logical that if you have asthma, you need to take some drug to reduce the inflammation of those tubes, so you can breathe. Indeed, billions of dollars in "anti-asthmatic" drugs are sold. This is obviously NOT a cure of asthma, but a very temporary remedy for the natural inflammation that the body is using to try to heal the body.
Inflammation: The Leukocyte Adhesion Cascade
Inflammation is a defense reaction caused by tissue damage or injury, characterized by redness, heat, swelling, and pain. The primary objective of inflammation is to localize and eradicate the irritant and repair the surrounding tissue. For the survival of the host, inflammation is a necessary and beneficial process. The inflammatory response involves three major stages: first, dilation of capillaries to increase blood flow; second, microvascular structural changes and escape of plasma proteins from the bloodstream; and third, leukocyte transmigration through endothelium and accumulation at the site of injury.
The leukocyte adhesion cascade is a sequence of adhesion and activation events that ends with extravasation of the leukocyte, whereby the cell exerts its effects on the inflamed site. At least five steps of the adhesion cascade are capture, rolling, slow rolling, firm adhesion, and transmigration. Each of these five steps appears to be necessary for effective leukocyte recruitment, because blocking any of the five can severely reduce leukocyte accumulation in the tissue. These steps are not phases of inflammation, but represent the sequence of events from the perspective of each leukocyte. At any given moment, capture, rolling, slow rolling, firm adhesion and transmigration all happen in parallel, involving different leukocytes in the same microvessels.
The roles of adhesion molecules in acute and chronic inflammation have been investigated using in vitro model systems and in vivo microcirculation studies. The ultimate goal of inflammation research is to develop methods to control inflammation by modulating or blocking leukocyte adhesion to the endothelium. These ideas developed by basic research contribute to contemporary research projects developing anti-inflammatory drugs. Anti-inflammatory agents function as blockers, suppressors, or modulators of the inflammatory response.
The inflammatory response begins with a release of inflammatory chemicals into the extracellular fluid. Sources of these inflammatory mediators, the most important of which are histamine, prostaglandins, and cytokines, are injured tissue cells, lymphocytes, mast cells and blood proteins. The presence of these chemicals promote and further the reactions to inflammation, which are redness, heat, swelling, and pain.
Anti-inflammatory drugs block or suppress the inflammatory response, preventing or reducing the appearance of adverse reactions to the irritant. Diseases and cases such as asthma, arthritis, organ transplants, and surgical trauma, for example, are treated with non-steroidal or steroidal anti-inflammatory agents. Aspirin and some other anti-inflammatory drugs exert their analgesic effects by inhibiting prostaglandin synthesis.
Click here for a description of non-steroidal anti-inflammatory drugs.
Click here for a description of steroidal anti-inflammatory drugs.
Non Steroidal Anti-Inflammatory Drugs (NSAIDs) are medications which, as well as having pain-relieving (analgesic) effects, have the effect of reducing inflammation when used over a period of time.
NSAIDs can be used as simple pain killers (analgesics), but paracetamol is usually preferable, as it is likely to have less unwanted effects, and costs less. They are most useful in conditions which cause inflammation. The anti-inflammatory effects may take from a few days to three weeks to come on, so it is worth persevering for a while before deciding that a NSAID is not going to help.
NSAIDs are used as follows:
The NSAIDs work by affecting some chemicals in the body which cause inflammation, the prostaglandins. Unfortunately the same group of chemicals are involved in the stomach, and so the NSAIDs tend to cause indigestion, and may even cause duodenal or stomach ulceration.
As a result of this side-effect they cannot be used in someone with a history of peptic ulcer, except in exceptional circumstances, under close medical supervision. Also they would rarely be used and, if used, only with extra care, in somebody with heartburn or indigestion.
In general, the more effective a NSAID is at reducing inflammation, the more likely it is to cause indigestion. Sometimes your doctor will prescribe them along with something to cut down the risk of ulceration. There is even one medication that contains both components together.
There have been recent advances, in that some NSAIDs are said to be more specific in dealing with inflammation and less likely to irritate the digestive (gastro-intestinal) system, but nothing has yet overcome this problem altogether.
The drugs vary in strength and side effects. Usually, as with other medications, the more effective they are, the more side-effects they are likely to have. Aspirin, which originated from willow bark, has been around for a long time and is in many people's medicine chests. This is an anti-inflammatory analgesic. Most NSAIDs also reduce the temperature in someone with a fever.
Of the newer medications in this group, the one in widest general use is Ibuprofen, which is available over the counter in many countries. There are a large number of other NSAIDs, most of which have to be obtained on prescription in the UK.
The one in most extensive use in UK, after Ibuprofen, is Diclofenac.
There are many other potential side effects, but these vary according to the drug chosen and the individual taking it. The other side effects are far less likely to occur.
Specific allergy to a NSAID can be quite dramatic, with rash, swelling of the face, and sometimes difficulty breathing. (If this happens you should call for help urgently.) As with other drugs, if you get a reaction which you suspect to be a side effect, stop taking it and check with your doctor. Sometimes, if the reaction involves an itchy rash and or swelling, it is worth trying an antihistamine in the meantime.
Some people with asthma react to the NSAIDs by getting more wheezy. If this happens you should stop the drug, and use your usual asthma medication, calling the doctor if this does not work.
NSAIDs cannot be used (are contraindicated) in the following cases:
Care is needed if you have:
These drugs are available in nearly every form:
Although non-oral routes of administration avoid the direct irritation of the stomach, they do not avoid the indigestion and ulcer risks, as these are caused by the chemical once it is in the blood stream.
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Persistent
asthma is an inflammatory disease that requires
regular anti-inflammatory therapy1