Effects of stress-dose hydrocortisone therapy in septic shock (part III): monocyte HLA-DR expression and blood interferon-? concentration. Preliminary results of a double blinded, randomized, placebo-controlled cross-over study

Background

Immunoparalysis, defined as a decreased level of human Ieukocyte antigen (HLA)-DR receptor expression on monocytes, correlates with the severity of septic shock and outcome [1].

Hydrocortisone (HC) alters the immune response at almost all levels and is considered to suppress HLA-DR expression on monocytes. IFN-? as a potent activator of mononuclear phagocytes increases the ability of monocytes to express HLA-DR in vitro and in vivo. One of the aims of our study was to analyzeimmunosuppressive effects of HC stress-dose therapy in septic shock patients. Here we present results of an interim analysis of the first 20 patients enrolled in the study.

Methods

The study was designed as a double blinded, randomized, cross-over, placebo-controlled trial in 40 patients. Patients who fulfilled the criteria for septic shock according to the Consensus Conference on Sepsis and Organ Failure [2] received a dose of 10 mg/h hydrocortisone after an initial loading dose of 100 mg, or placebo for 3 days. After 3 days, patients from the HC-group switched to the placebo-group and vice versa. Blood samples were obtained before the study and daily for a period of 6 days. A whole blood flow-cytometry analysis was performed to analyze monocyte HLA-DR antigen expression. Plasma IFN-? levels were measured by an enzyme-linked immunoassay.

Results

There were no striking differences in monocyte HLA-DR expression between patients who received HC or placebo (Fig. 1). However, compared to baseline values, a transient decrease of HI.A-DR expression was observed in the group which received HC early. INF-? increased in both groups after start of the study, but returned to baseline in the placebo-group on day 3 (Fig. 2). In the follow-up, INF-? did not further increase in the placebo-group but noticeably in the HC-group.

Conclusion

Stress-dose HC treatment did not induce immunoparalysis in patients with septic shock during the study period. HLA-DR expression remained almost constant over the period of the trial which we postulate to be due to HC-induced increase of INF-? synthesis.

Figures 1-2.

Monocyte HLA-DR expression (Fig. 1) and IFN-gamma concentration (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.