Which of the following inflammatory mediator doesn't cause fever: March 2011
Ans. A: Nitric oxideNitric oxide derived from endothelium and macrophages leads to vascular smooth muscle relaxation and killing of microbes Fever is caused by IL-1, TNF and prostaglandinsPyrogensA 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 some bacteria, is an example of an exogenous pyrogen.Depyrogenation may be achieved through filtration, distillation, chromatography, or inactivation.Endogenous pyrogensIn essence, all endogenous pyrogens are cytokines, molecules that are a pa of the innate immune system.They are produced by phagocytic cells and cause the increase in the thermoregulatory set-point in the hypothalamus.Major endogenous pyrogens are interleukin 1 (alpha and beta), interleukin 6 (IL-6), prostaglandins and tumor necrosis factor-alpha.Minor endogenous pyrogens include interleukin-8, tumor necrosis factor-alpha, tumor necrosis factor-beta, macrophage inflammatory protein-alpha and macrophage inflammatory protein-beta as well as interferon-alpha, interferon-beta, and interferon-gamma.These cytokine factors are released into general circulation, where they migrate to the circumventricular organs of the brain due to easier absorption caused by the blood-brain barrier's reduced filtration action there.The cytokine factors then bind with endothelial receptors on vessel walls, or interact with local microglial cells.When these cytokine factors bind, the arachidonic acid pathway is then activated.Exogenous pyrogensOther mechanism of fever caused by exogenous pyrogens includes 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 endogenous cytokine factors, such as interleukin 1(IL-1), interleukin 6 (IL-6), and the tumor necrosis factor-alpha.In other words, exogenous factors cause release of endogenous factors, which, in turn, activate the arachidonic acid pathway.Pattern of fever:Continuous fever: Temperature remains above normal throughout the day and does not fluctuate more than 1 degC in 24 hours, e.g. lobar pneumonia, typhoid, urinary tract infection, brucellosis, or typhus. Typhoid fever may show a specific fever pattern, with a slow stepwise increase and a high plateau.Intermittent fever: The temperature elevation is present only for a ceain period, later cycling back to normal, e.g. malaria, kala-azar, pyaemia, or septicemia. Following are its types:- Quotidian fever, with a periodicity of 24 hours, typical of Malaria- Teian fever (48 hour periodicity), typical of Malaria- Quaan fever (72 hour periodicity), typical of Plasmodium malariae.Remittent fever: Temperature remains above normal throughout the day and fluctuates more than 1 degC in 24 hours, e.g., infective endocarditis.Pel-Ebstein fever: A specific kind of fever associated with Hodgkin's lymphoma, being high for one week and low for the next week and so on.A neutropenic fever, also called febrile neutropenia, is a fever in the absence of normal immune system function. Because of the lack of infection-fighting neutrophils, a bacterial infection can spread rapidly; this fever is, therefore, usually considered to require urgent medical attention. This kind of fever is more commonly seen in people receiving immune-suppressing chemotherapy than in apparently healthy people.Febricula is an old term for a low-grade fever, especially if the cause is unknown, no other symptoms are present, and the patient recovers fully in less than a weekNitric oxideIt is also known as the 'endothelium-derived relaxing factor', or 'EDRF'It is biosynthesized endogenously from L-arginine, oxygen and NADPH by various nitric oxide synthase (NOS) enzymes.The endothelium (inner lining) of blood vessels uses nitric oxide to signal the surrounding smooth muscle to relax, thus resulting in vasodilation and increasing blood flow.Nitric oxide is highly reactive (having a lifetime of a few seconds), yet diffuses freely across membranes.These attributes make nitric oxide ideal for a transient paracrine (between adjacent cells) and autocrine (within a single cell) signaling molecule.The production of nitric oxide is elevated in populations living at high altitudes, which helps these people avoid hypoxia by aiding in pulmonary vasculature vasodilation.Effects include vasodilatation, neurotransmission, modulation of the hair cycle, production of reactive nitrogen intermediates and penile erections (through its ability to vasodilate).Nitroglycerin and amyl nitrite serve as vasodilators because they are conveed to nitric oxide in the body.The vasodialating antihypeensive drug minoxidil contains an NO moity and may act as an NO agonist.Similarly, Sildenafil citrate, popularly known by the trade name Viagra, stimulates erections primarily by enhancing signaling through the nitric oxide pathway in the penis.Nitric oxide is also generated by phagocytes (monocytes, macrophages, and neutrophils) as pa of the human immune response.Nitric oxide can contribute to reperfusion injury when an excessive amount produced during reperfusion (following a period of ischemia) reacts with superoxide to produce the damaging oxidant peroxynitrite.
Nitric oxide
Prostaglandin
IL-1
TNF-alpha