Circulatory Immune Cells in Cushing Syndrome: Bystanders or Active Contributors to Atherometabolic Injury? A Study of Adhesion and Activation of Cell Surface Markers.

Glucocorticoids (GC) induce cardiometabolic risk while atherosclerosis is a chronic inflammation involving immunity. GC are immune suppressors, and the adrenocorticotrophic hormone (ACTH) has immune modulator activities. Both may act in atherothrombotic inflammation involving immune cells (IMNC). Aim . To investigate adhesion and activation surface cell markers (CDs) of peripheral IMNC in endogenous Cushing syndrome (CS) and the immune modulator role of ACTH. Material and Methods . 16 ACTH-dependent CS (ACTH-D), 10 ACTH-independent (ACTH-ID) CS, and 16 healthy controls (C) were included. Leukocytes (Leuc), monocytes (MN), lymphocytes (Lym), and neutrophils (N) were analyzed by flow cytometry for atherosclerosis previously associated with CDs. Results . Leuc, N, and MN correlated with CS ( p < 0.05), WC ( p < 0.001), WHR ( p = 0.003), BMI ( p < 0.001), and hs-CRP ( p < 0.001). CD14++ CD16+ ( p = 0.047); CD14+ CD16++ ( p = 0.053) MN; CD15+ ( p = 0.027); CD15+ CD16+ ( p = 0.008) N; and NK-Lym ( p = 0.019) were higher in CS. CD14+ CD16++ MN were higher in ACTH-ID (8.9 ± 3.5%) versus ACTH-D CS (4.2 ± 1.9%) versus C (4.9 ± 2.3%). NK-Lym correlated with c-LDL ( r  = 0.433, p = 0.039) and CD15+ N with hs-CRP ( r  = 0.446, p = 0.037). In multivariate analysis, Leuc, N, and MN depended on BMI ( p = 0.021), WC ( p = 0.002), and WHR ( p = 0.014), while CD15+ and CD15+ CD16+ N on hypercortisolism and CS ( p = 0.035). Conclusion . In CS, IMNC present changes in activation and adhesion CDs implicated in atherothrombotic inflammation. ACTH-IDCS presents a particular IMNC phenotype, possibly due to the absence of the immune modulator effect of ACTH.