A comparison of the acute inflammatory response in adrenalectomised and sham‐operated rats

Abstract

1 Carrageenin pleurisy was induced in adrenalectomised (ADX) and sham-operated (SHO) rats.2 The magnitude and duration of inflammation, as estimated by fluid exudation and cell migration, was greatly increased (approximately doubled) in ADX rats compared with that in their SHO controls.3 The content of eicosanoids (6-keto-prostaglandin Fl,, (6-keto-PGFIJ, thromboxane B2 (TXB2), and leukotriene B4 (LTB4)) in inflammatory exudates from ADX rats was significantly (2-4 fold) greater than that of their SHO controls. 4 Resident macrophages obtained from ADX rats produced more eicosanoids per cell per unit time when stimulated in vitro with zymosan, than did cells from the SHO controls. 5 Administration of glucocorticoids blocked the inflammatory response and reduced the release of eicosanoids both in vitro and in vivo in both groups of rats. 6 These data are consistent with the notion that physiological amounts of glucocorticoids exert a tonic inhibitory action on phospholipase activity in normal animals and that the increased secretion of these hormones during the inflammatory response serves to check and control the development of inflammation.

Glucocorticoid deficiency increases phospholipase A2 activity in rats.

“…The latter hypothesis was proposed in 1922 by Kepinov, who reported an increased sensitivity to bronchial anaphylactic reactions in ADX guinea pigs (16). That observation was in line with the later findings ofan association between glucocorticoid deficiency and disease states explained by allergic and/or immunological mechanisms in experimental animals and humans (17,(61)(62)(63)(64). The upregulation of group II PLA2 enzyme and the downregulation of lipocortin-I by low levels of glucocorticoids indicate that clinically unrecognized partial glucocorticoid deficiency, either caused by suppression of endogenous glucocorticoid production after withdrawal of exogenous glucocorticoids or caused low cortisol synthesis for other reasons, may be relevant for the genesis of inflammatory diseases.…”

“…Previous investigations have shown an increased duration and magnitude of inflammatory reactions and higher concentrations of various prostaglandins after adrenalectomy (ADX) or treatment with a glucocorticoid receptor antagonist in animals (16)(17)(18)(19)(20). It was hypothesized that the increased concentrations of prostaglandins were caused by an increased activity of PLA2 ( 17,20). In the present study, we report the effect of glucocorticoid deficiency induced by ADX in rats on mRNA, protein levels of group II PLA2, and total enzyme activity of PLA2 in different tissues.…”

An overview of the effects of annexin 1 on cells involved in the inflammatory process

“…It is worth noting that scenario no. 2 could also due, at least in part, by lack of activity of anti-inflammatory mediators, tonically active to down-regulate the pro-inflammatory phase (classical example being the one of glucocorticoids, in view of the exacerbation of the response observed after adrenalectomy (Flower et al 1986, Perretti et al 1989). …”

Inhibition of carrageenin‐induced rat paw oedema by crotapotin, a polypeptide complexed with phospholipase A2

“…Their anti-inflammatory effects are in part attributed to the synthesis of lipocortins, a family of glucocorticoid-induced proteins with anti-phospholipase activity (Flower, 1988). Lipocortins inhibit carrageenin-induced rat paw oedema presumably by preventing arachidonic acid mobilization from membrane phospholipids (Parente et al, 1984;Flower et al, 1986;Cirino et al, 1989). Our results showing that crotapotin inhibited carrageenin-induced oedema in adrenalectomized rats to the same extent as in sham-operated rats, clearly indicate that the anti-oedematogenic effect of crotapotin is independent of the release of endogenous corticosteroids.…”