Soluble Fas may be a proinflammatory marker after cardiopulmonary bypass in children.
OBJECTIVE
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.
Joashi
U
U
Department of Pediatric Intensive Care, Guy's Hospital, London, United Kingdom.
Tibby
S M
SM
Turner
C
C
Mayer
A
A
Austin
C
C
Anderson
D
D
Durward
A
A
Murdoch
I A
IA
D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage; D053222:Fas Ligand Protein; D005260:Female; D006330:Heart Defects, Congenital / Q000601:surgery; D006801:Humans; D007223:Infant; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D011446:Prospective Studies; D018746:Systemic Inflammatory Response Syndrome / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control; D019014:fas Receptor / Q000097:blood*
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D018836:Inflammation Mediators; D015850:Interleukin-6; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor; D003907:Dexamethasone