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Fever

Fever is the natural response to infection. Pyrexia Pyrexia refers to an increase in body temperature resulting in a fever. A person with a fever is said to be febrile. When the body temperature is not raised the person is described as being apyrexial (the prefix ‘a’ or ‘an’ always means without). It is the hypothalamus which regulates body temperature by comparing the temperature of the blood circulating through the structure with a set point, usually between 36.5-37oC. When blood temperature drops, the hypothalamus initiates mechanisms to increase body temperature; conversely when blood temperature rises above the set point, heat loss mechanisms are initiated. In a fever the set point is increased to a new higher setting. Cause of fevers Fevers are most commonly caused by infection but also occur after tissue damage which may be caused by trauma, surgery or disease processes. For example, pyrexia is not uncommon after a myocardial infarction when part of the myocardium is damaged by an occlusion of the coronary arterial blood supply. Neoplasm is another possible cause and fever may be an early sign of a developing cancer. Infection is caused by the presence of microorganisms, such as bacteria or viruses, in a tissue. As the presence of bacteria or viruses causes a febrile response these infectious agents are often referred to as exogenous pyrogens. Exogenous means the cause is from outside the body, the infection comes from the environment. ‘Pyro’ literally means fire or heat, ‘gen’ refers to genesis which means beginning, so a pyrogen is something which ‘begins heat’. Leucocytes (white blood cells) are able to detect the presence of infectious agents in a tissue. Upon detecting infection these white cells, especially the macrophages, respond by producing cytokines. Cytokines are hormones produced by individual cells which have the potential to affect other cells or tissues in the body. Two of the cytokines produced by macrophages in response to the presence of infection are interleukins (ILs) and tumour necrosis factor (TNF). It is the presence of these cytokines in the blood that increase the set point of the hypothalamus in order to generate a fever. Because these pyrogenic cytokines are released from the body’s own cells they are referred to as endogenous pyrogens. Fever increases immune function By being able to recognise these cytokines the hypothalamus becomes aware of the presence of infection or damaged tissue. This allows for the initiation of a fever as part of the systemic response to infection. It has been suggested that pathogenic microorganisms are less viable at febrile temperatures. While there is some truth in this for some organisms, the main reason fever is generated is to increase the efficiency of the immune system. It has been demonstrated that neutrophils exhibit greater motility and bacterial killing activity as the temperature rises from 36 up to 40oC. Some studies indicate that macrophages function more efficiently at about 39oC. As neutrophils and macrophages are the most active phagocytic cells it follows that this process of white cells ‘eating’ bacteria and viruses works most efficiently at these increased temperatures. At temperatures around 39oC other activities of the immune system such as release of interferons, release of cytokines, activation of complement and the activity of lymphocytes have all been shown to be enhanced. Pyrexial temperatures also increase the likelihood that virally infected cells will self destruct, therefore killing the viral particles they contain. If the immune system is working more efficiently as a result of a fever, then the infection will be combated more aggressively and quickly. This will in turn limit the course of the infection, promoting rapid recovery. As infection is efficiently combated by the immune system in febrile patients, tissue damage as a result of the infection is less likely to occur. In addition to these benefits of fever there will also be an increase in the metabolic rate of the body which will allow tissues to regenerate more rapidly.