inflammation

inflammation The word incorporates the Greek for flame, and indeed an inflamed body part may feel ‘on fire’. In its traditional clinical description, inflammation has four characteristics: calor (heat), rubor (redness), tumor (swelling and dolor (pain). They are the manifestations of the body's defence against injury or against invasion by foreign material or microorganisms, including the means of removal or destruction of the offending agent, restriction of the spread of infection, and preparations for the healing process. But the immune system that implements vital self-preservation may also sometimes cause inflammation by misdirected attack on some part of the body itself.

Inflammation can occur anywhere, acutely in the skin around a wound or a sting, or in less visible sites such as the lining of the middle ear, or of the bladder, or of the gall bladder. Chronically it can be related to persistent infection, ulceration, mechanical or chemical irritation, or autoimmune disease. Wherever inflammation occurs there are certain local mechanisms in common, despite differences in the precipitating factors and also in the relative prominence of the four cardinal features. Even with relatively minor and apparently localized problems, there are whole-body responses. Wherever inflammation is located, the condition is given a name ending in-itis, prefixed by the traditional name of the body part, such as arthritis for the joints, gastritis for the stomach, pericarditis for the membranes around the heart, ileitis for the small intestine, osteitis for bone, encephalitis for the brain.

Tissue damage results in the release by cells of various chemical agents, including prostaglandins. Vasodilator substances relax the blood vessels in their vicinity and the resulting increase in blood flow accounts for the redness and heat; swelling follows from increased permeability of blood vessels. This all enhances the supply of factors normally present in the blood that are important for the inflammatory response, including white blood cells and certain proteins in the plasma. Locally released substances (cytokines), as well as bacterial toxins if there is infection, attract cells of the immune system — macrophages and lymphocytes.

The nerves that carry the signals, set up by chemical and mechanical stimulation of sensory receptors, that we perceive as pain, themselves in turn promote an increase in local blood flow through the axon reflex mechanism. The nerve fibres (axons) give off branches back to their site of origin, and these release ‘substance P’, a peptide that relaxes the vessel walls. This, together with prostaglandins and other substances released from damaged tissues and also from the macrophages that congregate at the site, increases the sensitivity of sensory nerve endings, enhancing pain.

The events are not confined to the focus of trouble. Cytokines circulating in the blood provoke diverse whole-body responses. A major site of action is the hypothalamus, where they can affect its regulation of pituitary secretions, of sympathetic nervous system activity, and of body temperature. Whilst the resulting responses mainly promote the many aspects of defence, some also modify reactions that might otherwise be excessive: endorphin release modifies pain, and the increase in secretion of corticosteroids has anti-inflammatory effects, including toning down the activity of macrophages and interfering with prostaglandin synthesis.

The manifestations of inflammation vary greatly with the nature and severity of the insult and whether the process is rapidly or slowly developing. It can be simply serous, with fluid exudation, such as in a blister or a swollen joint, or in the rhinitis (of the nose) at the start of a common cold. With some types of infection it can be suppurative, where tissue and immune cell debris form a collection of pus; and chronic inflammation can be granulomatous, with nodules composed of packed inflammatory cells.

The phenomena of inflammation reflect an appropriate response to infection, or to mechanical damage either by acute injury or prolonged pressure or friction. When they occur inappropriately as a reaction against the body's own tissues the manifestations are similar. Thus conditions that might be called ‘inflammatory’ may refer to chronic infections, or to degenerative processes (as in osteoarthritis), or they may result from congenital abnormalities (as in cystic fibrosis) or autoimmune disease (such as rheumatoid arthritis or regional ileitis (Crohn's disease)).

It would be inappropriate to attempt by treatment to diminish the body's responses, in terms of both local and widespread effects, if and when they were entirely appropriate and necessary to contain or cure the condition. Alleviation of the pain of inflammation by analgesic drugs is clearly beneficial to the sufferer; otherwise the first concern of treatment is if possible to remove the cause (such as treating infection by antibiotics, or removing foreign material). Other treatments in recent decades have been directed against inflammation itself, in conditions related to injury, ‘wear-and-tear’, and auto-immunity. Imitation and enhancement of the body's own anti-inflammatory corticosteroids became possible with synthetic steroid preparations, but there are undesirable side-effects. Along with the understanding of the role of prostaglandins in the mediation of inflammation and fever, a whole family of ‘non-steroidal antiflammatory drugs’ (NSAIDS) were developed, and they are widely used for a variety of muscle and joint problems, from accidental sprains to widespread arthritis. These drugs inhibit enzymes necessary for formation of prostaglandins, thus diminishing their local and general effects. (aspirin was well known to be useful in this context long before it was known to act by this mechanism.) No evidence has emerged for any positive or negative effect on the progress of the underlying conditions themselves (as opposed to relief of the symptoms), supporting the notion that the body's inflammatory responses are not always useful. Symptoms may indeed be relieved, but there are side-effects of NSAIDS, particularly gastrointestinal complications, related to the inhibition of prostaglandin synthesis where and when it is normally needed.

Sheila Jennett

See also autoimmune diseases; fever; immune system; infection; infectious diseases; injury; pain; prostaglandins.