Danon A, Prajgrod G
Dept. of Clinical Pharmacology, Corob Center of Health Sciences, Ben-Gurion University, Beer Sheva, Israel.
Agents Actions. 1991 Nov;34(3-4):416-23. doi: 10.1007/BF01988738.
Prostaglandins (PGs) are believed to be involved in some of the manifestations of the acute phase response, which may be triggered by bacterial lipopolysaccharide (LPS). Glucocorticoids are part of this response and, among other things, regulate PG synthesis and are anti-inflammatory. We investigated the role of endogenous and exogenous glucocorticoids in the regulation of aortic prostacyclin synthesis and in its response to LPS. Rats were injected with LPS and their aorta incubated ex vivo. Aortic prostacyclin (PGI2) production declined 1 h after LPS injection and remained low for at least 96 h. On the other hand, LPS stimulated PGI2 production in adrenalectomized rats, although the latter had reduced capacity to synthesize PGI2, compared with sham-operated rats. Dexamethasone substitution restored synthesis. In intact rats only acute (2 h), but not repeated administration of dexamethasone, increased PGI2 production. In vitro IL-1 alpha stimulated aortic PGI2 synthesis. It is concluded that glucocorticoids may exert a biphasic influence on aortic PGI2 production, possibly through a dual action of lipocortins. Moreover, it is suggested that lipocortin requires activation before it can exert its full effect, and that agonists such as LPS may provide the stimulus for such activation.
前列腺素（PGs）被认为参与了急性期反应的某些表现，急性期反应可能由细菌脂多糖（LPS）触发。糖皮质激素是这种反应的一部分，除其他作用外，还调节PG合成且具有抗炎作用。我们研究了内源性和外源性糖皮质激素在调节主动脉前列环素合成及其对LPS反应中的作用。给大鼠注射LPS，然后将其主动脉离体培养。LPS注射后1小时，主动脉前列环素（PGI2）生成量下降，并至少在96小时内维持在低水平。另一方面，LPS刺激了肾上腺切除大鼠的PGI2生成，不过与假手术大鼠相比，后者合成PGI2的能力有所降低。地塞米松替代可恢复合成。在完整大鼠中，仅急性（2小时）给予地塞米松可增加PGI2生成，而重复给药则无此作用。体外实验中，白细胞介素-1α刺激主动脉PGI2合成。结论是，糖皮质激素可能通过脂皮质蛋白的双重作用，对主动脉PGI2生成产生双相影响。此外，提示脂皮质蛋白在发挥其全部作用之前需要激活，而诸如LPS等激动剂可能提供这种激活的刺激。
