Extracellular TRX has been reported to reduce interleukin 1-beta expression by monocyte-macrophages in inflammatory conditions [7]. In addition, circulating TRX suppresses neutrophil chemotaxis http://www.selleckchem.com/products/azd9291.html [44]. More recently, it has been suggested that the anti-inflammatory mechanisms of TRX could be mediated, at least in part, by migration inhibitory factor (MIF) downregulation [45]. However, in septic conditions, TRX and MIF plasma levels showed a strong correlation, suggesting that pro- and anti-inflammatory agents are balanced to maintain homeostasis [46].In the present study, we confirm the limited interest of AOPP measurement and thiol content determination in acute setting, at least after CA, despite their place in experimental conditions [5,6].
On the contrary, high CRP and PCT levels are consistent with previous findings suggesting the overwhelming impact of systemic inflammation [4]. Overall, these results enhance the value of TRX after CA.Despite the large number of post-CA patients enrolled, some limitations of this study need consideration. First, we considered a retrospective single-institution cohort. However, all analyzed data were prospectively collected, and medical management was homogeneous. Second, this is a merely observational study, allowing only association rather than causation conclusions. Third, the utility of TRX to predict death was evaluated as a single parameter, without combination of TRX level to clinical or biological data that may have improved the overall prognosis value.
Fourth, measurement of other oxidative stress parameters, like MIF or manganese superoxide dismutase (MnSOD), or main inflammatory cytokines would have provided further mechanistic tracks. Similarly, determination of the TRX interacting protein (TXNIP) could give valuable data to help explain the TRX kinetics after CA. However, TXNIP is an intracellular protein that cannot be routinely measured in serum samples. Fifth, CA has the particularity of exhibiting two main causes of ICU death, that is, shock and neurological damage with subsequent care withdrawal. As inflammation and oxidative stress are expected to be greater in case of shock, subanalysis focused on this last group. Finally, the vast majority of patients underwent therapeutic hypothermia. If the relationship between inflammatory cytokines or biomarkers and effect of therapeutic hypothermia is controversial [4,25], the influence of hypothermia on TRX is as yet, unknown.
As the vast majority of our patients were treated by hypothermia, we could not perform a meaningful analysis of the impact of temperature on TRX levels. Similarly, there is no data about clearance of TRX during renal replacement therapy, which is widely applied in post-cardiac arrest survivors. To note, we report a high proportion of patients experiencing post-resuscitation shock. This is related to the study design, including Batimastat all consecutive patients and in particular those dying within 24 hours.