Fever induction mechanism

The mechanism of fever induction has been studied most extensively. The brain is protected from the potentially harmful effects of biologically active substances or cells in the circulation by the blood-brain barrier, which is manifested by the extremely tight junctions between the endothelial cells lining blood capillaries,48 which prevent circulating substances of a particular size and chemical property (as well as cells) from entering the brain. Proinflammatory cytokines are of a sufficiently large size that makes it unlikely that they can pass the blood-brain barrier. However, numerous pathways to explain how cytokines produced in the periphery can influence central nervous system events have been studied. For example, highly localized... 

It was observed that rats with a transient MCA occlusion have a larger brain infarction when recombinant human IL-1 P is injected into the lateral ventricle immediately after reperfusion [7,41]. Similar results have been obtained in rats with a permanent MCA occlusion [7,42]. The intraventricular injection of recombinant human IL-1 p also enhances the formation of brain edema and increases both the number of neutrophils in ischemic areas and neutrophil-endothelial cell adhesion. The most widely recognized functions of IL-1 appear to be the induction of endothelial cell adhesion molecule expression and the promotion of neutrophil tissue infiltration [7,41]. These observations suggest that IL-1 may play a deleterious role in cerebral ischemia. Studies showing a reduction in infarct size after the administration of IL-1 antagonists or inhibitors provide further evidence of the importance of IL-1 in cerebral ischemia [41,43-49]. The possible harmful mechanisms induced or activated by IL-1 include fever, increased heart rate and arterial blood pressure, enhancement of N-methyl-D-aspartate-mediated injury, proliferation of microglia, release of arachidonic acid, and stimulation of NO synthesis [7,50]. 

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