fever
fever - the febrile response to infections
why have a febrile response?
it is thought that the high body temperature in the febrile response helps fight off infections
the febrile mechanism is found in 5 of the 7 classes of vertebrates and it appears to be increasing in complexity with evolution so it is probably helpful to survival
earlier evolutionary species such as sharks and bony fish did not mount a fever physiologically but behaviourally moved into warmer environments to increase body temperature
reptiles evolved 350 mya and appear to be amongst the first to have developed a physiologic fever response based upon
cytokines in the blood acting on the hypothalamus
it appears rats and humans evolved a 2nd pyrogenic pathway to the hypothalamus - via the vagus nerve which activates local cytokines allowing for a much more rapid febrile response
optimal growth rates of Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli occur at a temperature range of 35-37degC, their growth rates drop dramatically at higher temperatures
1))
higher temperatures have been shown to denature pathogenic proteins and inactivate their toxins
as part of the inflammatory response, temperature elevation stimulates the release of histamines from mast cells and basophils that cause vessels to vasodilate allowing increased blood flow and transport of components of the nonspecific immune response - phagocytic macrophages, neutrophils, monocytes, and immunological NK cells
a temperature increase of 1degC increases the body's metabolism by 10-20% in what is called the Q10 Effect and increases rates of immunologic reactions
fever stimulates the release of leukocyte-endogenous mediator proteins into the bloodstream and digestive tract reducing free iron which retards bacterial growth as iron is needed for the cytochrome and electron-shuffling components of bacterial metabolism
2)
fever increases melatonin release which increases sleepiness and diverts energy to fighting the infection
3)
despite the above, there is actually little evidence that fever does improve survival
physiology
current concepts
the febrile response is initiated by the presence of a pyrogen which is typically an infectious organism or toxin by-product (eg. bacterial lipopolysaccharide (LPS)) from the infection, but can also be tissue trauma, blood products and certain medications
Toll-like receptor 4 appears to be involved in certain pyrogens such as LPS
the body produces a wide array of pyrogenic cytokines such as interleukins (IL-1beta, IL-6), interferon, and tumour necrosis factor alpha and perhaps complement factor 5a and platelet-activating factor, are carried to the blood-brain-barrier (BBB) in the blood
the endothelial and perivascular cells of the BBB, detects the circulating pyrogenic cytokines and starts prostaglandin synthesis, especially prostaglandin E2
5)
effector pathways of fever start from PGE2-EP3 receptor-bearing preoptic neurons
these neurons have been found to project to the raphe pallidus, where premotor sympathetic neurons driving thermogenesis in the brown fat and skin vasoconstriction are located and temperature is then based upon a balance of active and passive processes rather than the previous notion of a hypothalamic “setpoint”
inflammatory signaling and thermoeffector pathways involved in fever and hypothermia are modulated by neuropeptides and peptide hormones
?roles of leptin, orexins, arginine vasopressin, angiotensin II, and cholecystokinin
various autonomic, endocrine, and behavioural processes are then activated to raise the body temperature such as:
thermogenesis using brown fat
skin vasoconstriction
shivering
increased secretion of thyroxine
perception of being cold ⇒ increased clothing, heaters, blankets
the vagal pathway hypothesis
adverse consequences of fever
fever.txt · Last modified: 2014/05/11 18:49 (external edit)