Effect of Steroids during <i>Escherichia col</i><i>i</i> Endotoxinaemia in Rabbits

Abstract

A study was carried out on the effect of high doses of methylprednisolone to rabbits in combination with or after challenging them with Escherichia coli endotoxin. The animals given steroids simultaneously with the endotoxin or 2–6 h thereafter all had significantly higher white cell counts 24 h after endotoxin infusion. A second dose of endotoxin given 24 h after the first caused a rapid fall in white cell count, and no difference between the groups could then be observed 2 h later.The most striking effect was observed when methylprednisolone was administered simultaneously with the endotoxin. This caused a suppression of the clearance of endotoxin from the circulation, and this in turn could probably account for some newly synthesized thromboplastin expressed by the circulating monocytes. Furthermore, monocyte activation appears to be significantly higher in the animals receiving steroids than in the controls when the animals are subjected to two doses of endotoxin injections 24 h apart. Thus, high doses of methylprednisolone cannot be seen to have any beneficial effect as judged from the parameters tested in the present study.

The Tissue Factor Pathway in Disseminated Intravascular Coagulation

“…However, when the animals were given another equal dose of LPS 24 hours after the first one, a dramatic increase in TF in circulating monocytes over the subsequent 2 hours followed, reaching a level three to four times higher than after the first LPS shot. 101 In our whole blood ex vivo model, methylprednisolone caused about 70 to 80% inhibition of LPSinduced TF and TNF in monocytes, 102 corroborative evidence of the earlier observation that glucocorticosteroids have a potent inhibitory effect on monocyte/ granulocyte stimulation in inflammatory reactions. 103,104 In striking contrast to the dampening effect of corticosteroids thus seen in our whole blood model, when rabbits were given a dose of glucocorticoids the day before LPS was injected, the subsequent rise in TF in circulating monocytes was increased several times compared with controls not subjected to the hormone.…”

“…103,104 In striking contrast to the dampening effect of corticosteroids thus seen in our whole blood model, when rabbits were given a dose of glucocorticoids the day before LPS was injected, the subsequent rise in TF in circulating monocytes was increased several times compared with controls not subjected to the hormone. 101,105 The extent of TF expression in monocytes correlated well with the degree of sickness to which the animals succumbed. These results appeared to be in line with those from studies on the usage of high doses of steroids in human cases of infectious disease and septic shock, in which steroid administration was associated with increased mortality, often because of secondary infection.…”

Dexamethasone enhances LPS induction of tissue factor expression in human monocytic cells by increasing tissue factor mRNA stability

“…In contrast, Dex enhances LPS induction of TF expression in human monocytes and monocytic THP-1 cells [18]. Similarly, leukocytes isolated from rabbits presensitized with glucocorticoids before injection with LPS expressed higher levels of procoagulant activity than leukocytes from rabbits given LPS alone [19,20]. However, unlike monocytic cells, Dex did not enhance LPS induction of TF expression in endothelial cells [18].…”