The Th17/Treg imbalance in patients with cardiogenic shock

Type 17 helper T (Th17) cells producing the proinflammatory signature cytokine interleukin (IL)-17 are conterregulated by regulatory T cells (Treg) producing anti-inflammatory cytokines like transforming growth factor (TGF)-β and interleukin-(IL)-10. An imbalance of the Th17/Treg-ratio toward Th17 cell subset was shown to be involved in plaque destabilization and acute myocardial infarction (AMI), while no data exist in infarction-related cardiogenic shock (CS). The objective of this study was to evaluate the role of Th17/Treg and their related cytokines in uncomplicated AMI and infarction-related CS.

In an observational monocentric study, blood sample from age-matched healthy controls (HC, n = 20), patients with uncomplicated AMI (n = 20), patients with CS who survived for at least 28 days (CS-survivors, n = 20) and CS-non-survivors (n = 20) were analyzed. Circulating Th17 and Treg cell subsets and their intracellular cytokine expression were measured by flow cytometry and associated with circulating proinflammatory Th17-derived cytokines IL-6, IL-17 and their anti-inflammatory Treg-derived cytokines TGF-β and IL-10 measured by enzyme immunoassay. According to the severity of ACS, CS-non-survivors showed the highest levels of Th17 (p < 0.001) and the lowest levels of Treg cells (p < 0.001) favoring a Th17/Treg imbalance toward the proinflammatory Th17 response (p < 0.001). Changes of T cell subsets were also associated with a proinflammatory cytokine expression measured by increased IL-6 (p < 0.001) and IL-17 levels (p < 0.001) and decreased TGF-β (p < 0.001) and IL-10 levels (p = 0.057). For the Th17/Treg-ratio at admission, a cut-off point of >0.33 had a sensitivity of 90 % and a specificity of 80 % to determine 28-day mortality in CS (confirmed by ROC analysis, area under the curve: 0.88 ± 0.06, p < 0.001). Th17/Treg-ratio >0.33 was observed to be an independent predictor for 1-year mortality in CS confirmed by Cox proportional hazard analysis (hazard ratio (HR): 4.31; 95 % confidence interval (CI) 1.44-12.93; p = 0.009).

The Th17/Treg imbalance toward a Th17 shift might represent a promising candidate as therapeutic target and risk indicator in cardiogenic shock.