Serum macrophage migration inhibitory factor reflects adrenal function in the hypothalamo-pituitary-adrenal axis of septic patients: an observational study

Abstract

Background: The hypothalamo-pituitary-adrenal (HPA) axis modulates the inflammatory response during sepsis. Macrophage migration inhibitory factor (MIF), which counteracts the anti-inflammatory activity of glucocorticoid (GC), is one of the mediators of the development of inflammation. An inflammatory imbalance involving GC and MIF might be the cause or result of adrenal insufficiency. Our objective was to clarify the relationship between serum MIF and adrenal function in the HPA axis of sepsis patients using the adrenocorticotropic hormone (ACTH) stimulation test.

Methods: An observational study was performed in a university intensive care unit over a two-year period. Of 64 consecutive sepsis patients, 41 were enrolled. The enrolled patients underwent an ACTH stimulation test within 24 h of the diagnosis of severe sepsis or septic shock. Clinical and laboratory parameters, including serum MIF and cortisol, were measured.

Results: Based on their responses to the ACTH stimulation test, the patients were divided into a normal adrenal response (NAR) group (n = 22) and an adrenal insufficiency (AI) group (n = 19). The AI group had significantly more septic shock patients and higher prothrombin time ratios, serum MIF, and baseline cortisol than did the NAR group (P < 0.05). Serum MIF correlated significantly with the SOFA (Sequential Organ Failure Assessment) score, prothrombin time ratio, and delta max cortisol, which is maximum increment of serum cortisol concentration after ACTH stimulation test (rs = 0.414, 0.355, and -0.49, respectively, P < 0.05). Serum MIF also correlated significantly with the delta max cortisol/albumin ratio (rs = -0.501, P = 0.001). Receiver operating characteristic curve analysis identified the threshold serum MIF concentration (19.5 ng/mL, P = 0.01) that segregated patients into the NAR and AI groups.

Conclusions: The inverse correlation between serum MIF and delta max cortisol or the delta max cortisol/albumin ratio suggests that high serum MIF reflects an insufficient adrenal response in the HPA axis. Serum MIF could be a valuable clinical marker of adrenal insufficiency in sepsis patients.

Figure 1

Study flow diagram. Sixty-four septic patients were assessed for their eligibility for this study. Of these, 23 were excluded and 41 were enrolled. All the enrolled patients underwent an ACTH stimulation test and were divided into two groups: the normal adrenal response group (NAR group) and the adrenal insufficiency group (AI group).

Figure 2

ROC curve of serum MIF concentration used to segregate patients into the NAR and AI group. The area under the curve was 0.734, and the maximum sensitivity and specificity were 0.737 and 0.773, respectively. The reference value for the segregation of patients into the two groups was 19.5 ng/mL (P = 0.01).