Soluble Fas may be a proinflammatory marker after cardiopulmonary bypass in children
U Joashi1, S M Tibby, C Turner
1Department of Pediatric Intensive Care, Guy's Hospital, London, United Kingdom.
Insights
Steroid pretreatment before cardiopulmonary bypass reduced interleukin 6 and soluble Fas levels, indicating soluble Fas may be a marker of inflammation. Soluble Fas ligand levels were unaffected by steroids but correlated with monocyte apoptosis.
Area of Science:
- Cardiovascular Surgery
- Immunology
- Pediatric Critical Care
Background:
- Cardiopulmonary bypass (CPB) triggers inflammatory responses and apoptosis.
- Steroids can attenuate CPB-induced inflammation.
- Soluble Fas and soluble Fas ligand (sFasL) are implicated in inflammation and apoptosis, but their role post-CPB is unclear.
Purpose of the Study:
- To determine the temporal profiles of sFas and sFasL after CPB.
- To investigate the effect of steroid pretreatment on these profiles.
- To explore the relationship between sFas/sFasL and inflammatory markers.
Main Methods:
- Prospective, non-randomized study of 27 infants undergoing CPB.
- 13 infants received dexamethasone pretreatment.
- Measured sFas, sFasL, and interleukin-6 (IL-6) at various time points.
Main Results:
- Dexamethasone attenuated IL-6 and sFas release post-CPB.
- sFas levels mirrored IL-6, correlating with capillary leak markers.
- sFasL levels were unchanged by CPB or steroids, but higher levels correlated with monocyte count changes.
Conclusions:
- sFas and sFasL exhibit distinct temporal profiles post-CPB.
- sFas may serve as a proinflammatory marker, similar to IL-6, and is reduced by steroids.
- sFasL's role in apoptosis post-CPB warrants further investigation.
Objectives:
Ischemia-reperfusion injury after cardiopulmonary bypass is known to provoke an inflammatory response, which can be attenuated with steroid pretreatment. Cardiopulmonary bypass is also known to stimulate apoptosis. Induction of the cellular apoptotic cascade occurs via interaction between two membrane receptors: Fas and Fas ligand. Both molecules also exist in soluble forms, whose significance remains undetermined; however, both may have a proinflammatory role. We aimed to document the temporal profile of soluble Fas and soluble Fas ligand after cardiopulmonary bypass and to investigate whether steroid pretreatment alters this response.
Methods:
The study was of a non-randomized, non-blinded, prospective nature. Twenty-seven infants were monitored prospectively, of whom 13 received dexamethasone at induction of anesthesia. Soluble Fas, soluble Fas ligand, and interleukin 6 were measured from induction of anesthesia until 24 hours after admission to the intensive care unit. Data on clinical and laboratory variables were also collected at the same time intervals.
Results:
As expected, dexamethasone pretreatment attenuated interleukin 6 release and the clinical systemic inflammatory response after bypass. Soluble Fas showed a remarkably similar profile to interleukin 6, in terms of temporal release and attenuation with steroids. There was also a correlation between maximum soluble Fas and markers of capillary leak (colloid requirement and drain loss). Conversely, soluble Fas ligand release was unchanged by cardiopulmonary bypass and steroid administration. However, patients with higher soluble Fas ligand levels exhibited a more dramatic drop and delayed recovery in monocyte count, consistent with the role of this molecule in apoptosis.
Conclusions:
Release of soluble Fas and soluble Fas ligand follows a markedly different temporal profile after cardiopulmonary bypass. The similarity between soluble Fas and interleukin 6, together with the attenuation of both with steroids, may suggest a role for soluble Fas as a proinflammatory marker.
