Fever pyrogens

Pyrogenic A fever-producing substance. The presence of these substances is determined by the Limulus Amebocyte Lysate (LAL) test and measured in EU/ml (endotoxin units per milliliter). 

The inherent mechanism that prevents the height of fever from reaching a potentially dangerous level. It is mediated by substances liberated both systemically and within the brain during fever that counter the formation or action of endogenous pyrogens, or inhibit the activity of neural circuits that modulate febrigenesis. 

Fever. Table 3 Some common pathogenic stimuli that induce fever ( exogenous pyrogens )... 

Fever is the most common manifestation. The thermoregulatory centre in the hypothalamus regulates body temperature and this can be affected by endotoxins (heat-stable lipopolysaccharides) of Gram-negative bacteria and also by a monokine secreted by monocytes and macrophages called interleukin-1 (IL-1) which is also termed endogenous pyrogen. Antibody production and T-cell proliferation have been shown to be enhanced at elevated body temperatures and thus are beneficial effects of fever. 

One pyrogen test is a qualitative biological test based on the fever response of rabbits. If a pyrogenic substance is injected into the vein of a rabbit, a temperature elevation will occur within 3 hours. Many imitative medical agents will also cause a fever. 

Pyrogens are substances that, when they enter the blood stream, influence hypothalamic regulation of body temperature, usually resulting in fever. Medical control of pyrogen-induced fever proves very difficult, and in severe cases results in patient death. 

In many instances the influence of pyrogens on body temperature is indirect. For example, entry of endotoxin into the bloodstream stimulates the production of IL-1 (Chapter 9) by macrophages. It is the IL-1 that directly initiates the fever response (hence its alternative name, endogenous pyrogen ). 

Hartung, T., Comparison and validation of novel pyrogen tests based on the human fever reaction, ATLA, 30, 49, 2002. 

Disadvantages The protein expressed is accumulated within the cell matrix (intracellular) the protein does not undergo posttranslational modifications (resulting in proteins that may be structurally different or less useful to humans) the presence of lipopolysaccharides (pyrogens—microbial substances that cause fever) is likely to contaminate the product and there is a need for more extensive chromatographic purification. 

Pyrogens (e.g., bacterial matter) elevate—probably through mediation by prostaglandins (p. 196) and interleukin-1—the set point of the hypothalamic temperature controller (B2). The body responds by restricting heat loss (cutaneous vasoconstriction chills) and by elevating heat production (shivering), in order to adjust to the new set point (fever). Antipyretics such as acetaminophen and ASA (p. 198) return the set point to its normal level (B2) and thus bring about a defervescence. 

Inflammation/abscess formation at the site of injection Pyrogenic effect (fever)... 

The salicylates are also potent antipyretic agents, with the exception of diflunisal, which is only weakly active. Aspirin acts at two distinct but related sites. It decreases prostaglandin-induced fever in response to pyrogens and induces a decrease in interleukin-1 modulation of the hypothalamic control of body temperature. Thus, the hypothalamic control of body temperature returns, vasodilation occurs, heat dissipates, and fever decreases. Other uses of aspirin include inhibition of platelet aggregation via inhibition of thromboxanes, which has been shown to decrease the incidence of blood clots, myocardial infarction, and transient ischemic attacks. 

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