Effects of stress-dose hydrocortisone therapy in septic shock (part II): soluble E-selectin and interleukin-6. Preliminary results of a double blinded, randomized, placebo-controlled cross-over study

Background

E-selectin is a member of the selectin family, i.e. a transmembrane molecule which is essential for the adherence and extravasation of leukocytes. E-selectin is expressed by activated endothelial cells and interacts with circulating neutrophiles. IL-6 is a proinflammatory cytokine, produced by various cell tvpes. Both markers are elevated in the blood of patients with septic shock; E-selectin possibly plays a role in permeability alterations and organ damage, IL-6 is a predictor of outcome and severity. Stress-dose hydrocortisone improves the clinical situation of patients in septic shock. In vivo studies could show that corticosteroids inhibit the endothelial expression of adhesion molecules including E-selectin.

Methods

As a part of a double blind controlled cross-over study with stress dose hydrocortisone (10 mg/h) E-selectin and IL-6 levels were monitored for six days in 20 patients with septic shock. For the first 3 days patients received either hydrocortisone or placebo as a continuous intravenous infusion, for the next 3 days medication was switched. Blood was taken before starting and then once every day. Both IL-6 and E-selectin were measured by an ELISA technique.

Results

We found a decrease in IL-6 and E-selectin levels under application of hydrocortisone compared to the placebo group as 2 well as to the primary values. After switching to placebo, values increased again.

Conclusion

We could show that stress-dose hydrocortisone given to patients in septic shock markedly decreases soluble E-selectin and IL-6 levels. In addition to the hemodynamic effects of this therapy, there also seems to be an immunmodulating and anti-inflammatory effect, which might be organ protective.

Figures 1-2.

IL6 (Fig. 1) and E-selectin levels (Fig. 2) in septic shock patients, who received hydrocortisone therapy (see text). Day 0: before study. Data are presented as mean-values with SEM; n = 10 for each data point.