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P A R T 3  Drugs acting on the immune system

proteins. The lysosomal enzymes are an important part of biological recycling and the breakdown of once- living tissues after death. In the case of an inflammatory reaction, they can cause local cellular breakdown and further inflammation, which can develop into a vicious cycle leading to cell death. Many inflammatory diseases, such as rheumatoid arthritis and systemic lupus erythematosus, are examples of these uncontrolled cycles. The prostaglandins and leukotrienes are important to the inflammatory response because they act to moderate the reaction, thus prevent­ ing this destructive cycle from happening on a regular basis. Many of the drugs used to affect the inflamma­ tory and immune systems modify or interfere with these inflammatory reactions. Clinical presentation Activation of the inflammatory response produces a char­ acteristic clinical presentation. The Latin words calour,

tumour, rubor and dolour describe a typical inflamma­ tory reaction. Calour , or heat, occurs because of the increased blood flow to the area. Tumour , or swelling, occurs because of the fluid that leaks into the tissues as a result of the change in capillary permeability. Rubor , or redness, is related again to the increase in blood flow caused by the vasodilation. Dolour , or pain, comes from the activation of pain fibres by histamine and the kinin system. These signs and symptoms occur whenever a cell is injured (Figure 15.2). For example, if you scratch the top of your hand and wait for about a minute, the direct line of the scratch will be red (rubor) and raised (tumour). If you feel it gently, it will be warmer than the surrounding area (calour). You should also experience a burning sensation or discomfort at the site of the scratch (dolour). Invasion of the lungs by bacteria can produce pneumonia. If the lungs could be examined closely, they would also show the signs and symptoms of inflamma­ tion. They would be red from increased blood flow; fluid

Tissue injury

Exposure of plasma to injured cell, etc.

Release of histamine

Activation of Hageman factor

Prekallikrein Active kallikrein

Kininogen Bradykinin

Release of arachidonic acid

↑ Capillary permeability

Vasodilation

Leukotrienes (LTs) (LTB 4 , LTC 4 , LTD 4 , LTE 4 )

Prostaglandins (PGs) (PGI 2 )

Exudation of plasma proteins

↑ Blood flow

Oedema

Chemotaxis of leucocytes: Activation of neutrophils

Rubor (redness)

Calour (heat)

Dolour (pain)

Tumour (swelling)

Phagocytosis

Removal of debris and preparation of injured site for healing

FIGURE 15.2  The inflammatory response in relation to the four cardinal signs of inflammation.