Lack of effect of salicylate on pyrogen release from human blood leucocytes in vitro.
نویسندگان
چکیده
Although salicylates are widely used as antipyretic agents, the mechanism by which they lower body temperature is controversial. It has been suggested that these compounds act at peripheral sites of inflammation, by suppressing release of endogenous pyrogen from leucocytes exposed to an inflammatory stimulus (1), or by suppressing synthesis and release of fever-inducing prostaglandins (2, 3). Alternatively, considerable evidence in both man (4) and rabbits (5, 6) indicates that salicylates act centrally to lower fever by blocking the action of endogenous pyrogen on certain temperature-sensitive hypothalamic neurons. For example, stable fevers induced by infusions of leucocyte (endogenous) pyrogen in humans persisted for 50 min or so after the infusion was discontinued (4). However, when sodium salicylate was injected intravenously during the continuous pyrogen infusion, temperature fell promptly. This rapid antipyretic effect of salicylate is best explained by a central action rather than by altered production or release of pyrogen from the host's leucocytes. This postulated central action clearly does not exclude the possibility that these agents have peripheral antipyretic effects, as reported (1, 6). It seemed appropriate, therefore, to re-examine the action of salicylate on release of pyrogenic agents from leucocytes, with a model which approximates conditions of in vivo inflammation. The studies to be reported here indicate that salicylate does not suppress the release of pyrogen from human blood leucocytes following exposure to endotoxin or a phagocytic stimulus in vitro. By contrast, as expected, salicylate administered to rabbits suppressed fever to intravenous injection of endogenous pyrogen.
منابع مشابه
Observations on the Production of Pyrogenic Substances by Rabbit and Human Leucocytes
1. The mechanism of release of a pyrogen from leucocytes has been studied in cells obtained from sterile rabbit peritoneal exudates and from rabbit blood. Attempts were made to induce human leucocytes-from blood-to release a pyrogen. 2. Rabbit leucocytes, kept below 4 degrees C., were not pyrogenic and did not release any pyrogen when disintegrated. Incubating such cells, in various media, at 3...
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ورودعنوان ژورنال:
- The Yale Journal of Biology and Medicine
دوره 46 شماره
صفحات -
تاریخ انتشار 1973