2d. How is a fever initiated by the body?
Prostaglandin causes a fever. (explanation 1)Fever, which is mediated by a lipid called prostaglandin E2 (PGE2), can pass through multiple temperature phases. While it's well established that PGE2 originating in brain cells causes the second and later phases, the initial phase of fever has proven difficult to characterize. Of particular interest is whether fever onset is triggered by PGE2 that originates inside or outside the brain a question that has dogged researchers for nearly three decades. Now, Alexandre Steiner, Andrej Romanovsky, and colleagues provide evidence that PGE2 synthesis doesn't begin in the brain as previously thought, but in the lungs and liver. They also describe the molecular mechanismsthat produce PGE2 in these organs.(explanation 2)Temperature is ultimately regulated in the hypothalamus. A trigger of the fever, calleda pyrogen, causes a release of prostaglandin E2(PGE2). PGE2 then in turn acts on the hypothalamus, which generates a systemic response back to the rest of the body, causing heat-creating effects to match a new temperature level.In many respects, the hypothalamus works like a thermostat.When the set point is raised, the body increases its temperature through both active generation of heat and retention of heat. Peripheral vasoconstrictionboth reduces heat loss through the skin and causes the person to feel cold. Norepinephrineincreases thermogenesisin brown adipose tissue, and acetylcholinestimulatesmuscle to raise metabolic rate.If these measures are insufficient to make the blood temperature in the brain match the new set point in the hypothalamus, then shiveringbegins in order to use muscle movements to produce more heat. When the hypothalamic set point moves back to baseline either spontaneously or with medication, the reverse of these processes (vasodilation, end of shivering and nonshivering heat production) and sweating are used to cool the body to the new, lower setting.A pyrogen is a substance that induces fever. These can be either internal (endogenous) or external (exogenous) to the body. The bacterial substance lipopolysaccharide(LPS), present in the cell wall of gram-negative bacteria,is an example of an exogenous pyrogen. Pyrogenicity can vary: In extreme examples, some bacterial pyrogens known as superantigenscan cause rapid and dangerous fevers. Depyrogenationmay be achieved through filtration, distillation, chromatography, or inactivation.In essence, all endogenous pyrogens are cytokines, molecules that are a part of the immune system. They are produced by activated immune cellsand cause the increase in the thermoregulatory set point in the hypothalamus. Major endogenous pyrogens are interleukin 1(α and β)and interleukin 6(IL-6). Minor endogenous pyrogens include interleukin-8, tumor necrosis factor-β, macrophage inflammatory protein-α and macrophage inflammatory protein-β as well as interferon-α, interferon-β, and interferon-γ.Tumor necrosis factor-αalso acts as a pyrogen. It is
- Fall '12
- cells, immune cells