Inflammation basics

Acute inflammation is often beneficial

Inflammation is often an acute, localized and self-limiting protective response to trauma or microbial invasion that destroys, dilutes, or walls-off the injurious agent and injured tissue. It has been characterized in its gross form by the classic signs and symptoms of pain, heat, redness, swelling, and sometimes loss of function. Microscopically, it involves a complex series of events, including dilation of arterioles, capillaries, and venules, with increased permeability and blood flow, exudation of fluids, including plasma proteins, and leukocyte migration into the area of inflammation.

But even acute inflammation can be damaging

Acute inflammation is often beneficial but can also be detrimental to the host, depending on its cause, severity, duration and specific circumstances. For example, acute inflammation is often responsible for much of the permanent damage that occurs as a result of heart attacks and strokes. Acute inflammation can also exacerbate pre-existing conditions, such as by precipitating asthma attacks, migraine headaches or seizures in those suffering from the underlying malady.

Chronic inflammation is always detrimental

Whereas acute inflammation can be either beneficial or detrimental, chronic inflammation always involves detriment to the host. Chronic inflammation may result from an ongoing insult, or as a consequence of immune system dysfunction or dysregulation, or from some unknown cause. Effects of chronic inflammation can include scarring, tissue breakdown, and loss of function at the site of inflammation. It has also been associated with the development of certain cancers. The chronic inflammation that results from abnormal recognition of host tissue as foreign is a central feature in autoimmune disease such as systemic lupus erythematosus, rheumatoid arthritis and psoriasis. Conditions such as osteoarthritis and chronic back pain are also associated with chronic inflammation.

Subclinical (silent, systemic, low-grade) inflammation is a form of chronic inflammation (and chances are you’re suffering with it now)

Researchers now recognize that chronic inflammation may be present in a low grade, asymptomatic form for many years before its effects manifest as overt disease. This asymptomatic form of chronic inflammation is often referred to as subclinical inflammation (also silent inflammation, subacute inflammation, low grade inflammation, or systemic inflammation.) Subclinical inflammation can only be detected by laboratory tests or biochemical assays that assess levels of various markers of inflammation such as c-reactive protein, rheumatoid factor, anti-nuclear antibodies, cytokines, or other components, modulators or products of inflammation.

Subclinical inflammation is increasingly recognized as the cause of, or a substantial contributor to, a wide range of ailments, such as for example atherosclerosis, osteoarthritis, hypercholesterolemia, diabetes type 2, Alzheimer’s disease, some cancers, macular degeneration and a great many other ailments. Subclinical inflammation has been shown to increase disease risk, hasten disease onset and worsen disease prognosis. Subclinical inflammation is believed to increase the rate and severity with which signs and symptoms of aging appear.

A means of safely, effectively controlling (reducing) inflammation could have a major impact on global health

Collectively, inflammation in its various forms and manifestations is central to both the development and subsequent course of many ailments. Effective control of inflammation is therefore of paramount concern in the prevention, treatment, control and cure of disease – to reduce pain, suffering, disability and death.

Better therapies for the treatment of inflammation are urgently needed. Existing medications are often marginally effective or entirely ineffective, and their use is associated with frequent side effects that may be severe or even fatal.

Current medications have limited efficacy, but serious side effects

Current medications for inflammation generally fall into two broad categories: steroidal and non-steroidal drugs. Steroidal anti-inflammatory drugs include medications, such as cortisone, which are based on naturally occurring hormonal substances. Non-steroidal anti-inflammatory drugs (NSAIDs) include medications such as aspirin, ibuprofen, and naproxen.

NSAIDs are of limited efficacy but are nonetheless associated with significant side effects. NSAIDs have been known to cause, among other things, edema, stomach upset, stomach bleeding, stomach ulcers, kidney problems, kidney failure and hearing problems. The occurrence and severity of these side effects increases with prolonged use, which further limits their usefulness, especially as many of the conditions associated with inflammation are chronic conditions requiring long term treatment.

Steroidal drugs are generally more effective than NSAIDs but their systemic administration is associated with more frequent and more serious side effects. Steroidal drugs have been known to cause, among other things, loss of bone mass, thinning skin, cataracts, serious infection, weight gain, mood changes, psychiatric problems, hypertension, and bone marrow dysfunction. Clinicians must therefore use steroidal drugs only with great caution. Their side effects preclude long term systemic use except in the most serious conditions.

Osteoarthritis provides one example of why better medications are needed

As a simple illustration of the urgency with which better therapies for inflammation and its associated maladies are required, one need only consider osteoarthritis. The lack of a safe and effective treatment for inflammation means that perhaps 40 million Americans suffer daily with the pain and disability of osteoarthritis. Steroidal medications are not useful – the side effects are worse than the disease. As a result – and lacking a better alternative – millions rely on NSAIDs. NSAIDs provide only marginal relief for most, but their chronic use results in many thousands of hospitalizations and a substantial number of deaths each year.

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