Keep inflammation under control

Inflammation is the body's response to injury or infection and may be acute or chronic. Acute inflammation is the initial inflammatory response to, for example, burns, cuts, or more major trauma such as myocardial infarction (MI). Acute inflammation results in healing of the tissue when the injury or infection is removed. Symptoms include redness, swelling, heat or warmth, and pain and stiffness in the affected area. Chronic inflammation or prolonged inflammation is a continuous process of inflammation, tissue breakdown and repair attempts. This results in scarring and tissue destruction. Chronic inflammation results from bacterial infections and autoimmune diseases. In autoimmune disease, the inflammatory response is triggered when there are no stimuli and the immune system attacks itself.

The markers include mediators and inhibitors of inflammations and scavengers of potentially dangerous substances such as toxins. Classically, the protein changes include a rapid fall in serum albumin levels due to increased capillary permeability and the subsequent redistribution of albumin into the extravascular space. There is also a fall in prealbumin and transferrin levels, and increased a1- and a2-globulins as a result of increases of a1-antitrypsin, a1-acid glycoprotein and haptoglobin. In chronic inflammatory conditions and some malignancies, the a1-globulin level remains normal but the a2-globulin level is elevated and there may be a diffuse increase in gamma-globulins.

Serum protein electrophoresis is an insensitive method for monitoring the acute phase response. C-reactive protein (CRP) is an a2-globulin that is synthesised in the liver that can form cross-linked lattices, agglutinate, precipitate and activate the complement pathway. Despite being quantitatively a minor plasma protein, the increase in levels is detectable within 6 hours and the final increase may be as much as 60-fold. Thus, a raised level is unequivocal evidence of inflammation. It is also more specific than the erythrocyte sedimentation rate (ESR), therefore it is probably the most useful current measure of the acute phase response.
In general, the measurement of CRP is useful:

• in the face of symptoms and signs which are not specific for organic disease or
• when the acute phase response precedes the clinical changes of altered disease activity

Significant bacterial infections are unusual below 10mg/L except in neonates where 10-40mg/L typically represents mild inflammation but may be associated with severe viral infections and 40-200mg/L represents significant acute inflammation or bacterial infections. In burns or serious bacterial infections, levels may rise to 300mg/L or higher.

Many chronic inflammatory diseases are difficult to monitor clinically and serial CRP measurements can be valuable in assessing the response to therapy and changes in disease activity. This is particularly true of:

• rheumatoid arthritis
• polymyalgia
• giant cell arteritis
• systemic vasculitis and
• inflammatory bowel disease

When assessing the extent or activity of inflammation, the serum CRP level provides a rough guide to the amount of tissue involved in inflammation and to the integrity of the inflammatory response. Persistent elevation may indicate a poor prognosis in both inflammatory and malignant disease

Bacterial infection is the most potent activator of the acute phase response. A sudden rise in CRP may be a useful pointer to intercurrent sepsis, particularly where the kinetics of the acute phase response are known. For example:

• following major surgery
• those with little intrinsic response such as leukaemia, SLE and during peritoneal dialysis
• In all these cases there is a risk of silent but serious sepsis.
• Viral infections cause little acute phase response and the CRP measurement may be useful in indicating bacterial aetiology in
• meningitis
• neonatal illness
• pneumonia

Falling CRP levels are a useful indication of response to antibacterial therapy

Various studies have shown that a resting CRP greater than 3.5mg/L is associated with future coronary events in patient populations with unstable angina. Similarly, CRP levels above 7.0mg/L, recorded approximately six hours after coronary occlusion, are associated with a high mortality or a second infarction in the following 24 hours.

As well as being markers of inflammation, many of these proteins have specific roles and thus play an important part in the diagnosis, monitoring and treatment of pathological conditions.

• Pre-albumin is commonly employed to assess protein energy balance
• a1-antitrypsin level is used with a1-antitrypsin genotyping to assess a1-antitrypsin deficiency
• haptoglobin is often used to investigate intra-vascular haemolysis
• transferrin is commonly used to assess iron status
• immunoglobulins are commonly assessed in the investigation of immunodeficiency states and monoclonal bands.