Fever is said when there is an increase in internal body temperature to levels that are above normal (37°C, 98.6°F).
Temperature is regulated in the hypothalamus. Substances that induce fever are called pyrogens. These are both external or exogenous, such as the bacterial substance LPS, and internal or endogenous. The endogenous pyrogens (such as interleukin 1) are a part of the innate immune system, produced by phagocytic cells, and cause the increase in the thermoregulatory set-point in the hypothalamus. The endogenous pyrogens may also come directly from tissue necrosis.
One model for the mechanism of fever is the detection of lipopolysaccharide (LPS), which is a cell wall component of gram-negative bacteria. An immunological protein called Lipopolysaccharide-Binding Protein (LBP) binds to LPS. The LBP-LPS complex then binds to the CD14 receptor of a nearby macrophage. This binding results in the synthesis and release of various cytokine factors, such as interleukin 1 (IL-1), interleukin 6 (IL-6), and the tumor necrosis factor-alpha. These cytokine factors are released into general circulation where they migrate to the circumventricular organs of the brain, where the blood-brain barrier is reduced. The cytokine factors bind with endothelial receptors on vessel walls, or interact with local microglial cells. When these cytokine factors bind, they activate the arachidonic acid pathway. This pathway (as it relates to fever), is mediated by the enzymes phospholipase A2 (PLA2), cyclooxygenase-2 (COX-2), and prostaglandin E2 synthase (membrane-associated protein involved in eicosanoid and glutathione metabolism, also known as mPEGS-1). These enzymes ultimately mediate the synthesis and release of PGE2.
PGE2 is the ultimate mediator of the febrile response. The set-point temperature of the body will remain elevated until PGE2 is no longer present. PGE2 acts near the ventromedial preoptic area (VMPO) of the anterior hypothalamus and the parvocellular portion of the periventricular nucleus (PVN), where the thermal properties of fever emerge. It is presumed that the elevation in thermoregulatory set-point is mediated by the VMPO, whereas the neuroendocrine effects of fever are mediated by the PVN, pituitary gland, and various endocrine organs.
The brain ultimately orchestrates heat effector mechanisms. These may be
- increased heat production by increased muscle tone, shivering and hormones like epinephrine.
- prevention of heat loss, such as vasoconstriction.
The autonomic nervous system may also activate brown adipose tissue to produce heat (=non-exercise associated thermogenesis, also known as non-shivering thermogenesis), but this seems mostly important for babies. Increased heart rate and vasoconstriction contribute to increased blood pressure in fever.
I know it became little bit complicated, basic things is when pyrogens produce in the body through the blood circulation it reaches to the hypothalaus and reset the normal temperature to 37 degree centigrade and above and until and unless the body temperature is reached as set by the pyrogens body tries to conserve heat and tries to produce by chills and rigors thats how we get fever.
In most of the instances fever is a protective mechanism which tells us that our body heomostatis has been deraineged.
"never give up trying "
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