J Thorac Cardiovasc Surg 1995;110:286-287
© 1995 Mosby, Inc.
Early production of interleukin-10 during normothermic cardiopulmonary bypass
Monique Dehoux,
PhDa,e,
Ivan Philip, MDb,e,
Sylvie Chollet-Martin, PhDc,
Anne Boutten, PhDa,
Ulrich Hvass, MDd,
Jean-Marie Desmonts, MDb,e,
Geneviève Durand, PhDa
Laboratoire de Biochimie Aa
Department d'Anesthésie et Réanimationb
Laboratoire d'Hématologiec
Service de Chirurgie Cardiothoraciqued
INSERM U 408e
Hôpital Bichat—Claude Bernard
Paris, France
To the Editor:
Cardiopulmonary bypass (CPB) is known to cause a systemic inflammatory response associated with an increased production of proinflammatory cytokines (interleukin-1 [IL-1], IL-6, and IL-8).
1,2 Several studies suggest that IL-10 is an important factor in the down-regulation of inflammatory responses, in particular by inhibiting in vitro proinflammatory cytokine synthesis by neutrophils (PMN) and monocytes. 3 We hypothesized that IL-10 might be produced during CPB and could represent a regulatory mechanism controlling monocyte/PMN activation in vivo. We therefore measured plasma levels of IL-10 in comparison with that of IL-6 and IL-8 in patients undergoing cardiac operations with normothermic CPB.
Eight patients, 478 ± 8.9 years of age (mean ± standard error of the mean), were studied. Patients with corticosteroid therapy or suspected infectious diseases were excluded. Anesthesia and CPB management were performed as previously described. 2 Mean CPB and aorticclamping durations were 115 ± 9 and 89 ± 8 minutes, respectively (mean ± standard error of the mean). Serial blood samples were withdrawn from the radial artery catheter before sternotomy (T0), at the onset of CPB (H0), and at intervals of 1, 2, 4, 6, 10, and 24 hours (H1 to H24) after the onset of CPB. Blood samples were collected into sterile vacuum tubes with ethylenediaminetetraacetic acid, immediately centrifuged, and stored at -70º C. We measured IL-10 using an enzyme-linked immunosorbent assay that is specific for human IL-10 (EASIA Medgenix, Fleurus, Belgium) and IL-6 and IL-8 by enzyme-linked immunosorbent assays from Amersham (Biotrak, les Ulis, France).
As shown in Fig 1, whereas IL-10 was undetectable in any of the plasma samples at T0 and H0, plasma IL-10 levels rose in all of the patients as early as 1 hour after the onset of CPB, peaked either at H1 or H2 (H1, 76.2 ± 26.7 pg/ml; H2, 73.5 ± 24.8 pg/ml; mean ± standard error of the mean; p = 0.01 versus H0 by Wilcoxon's matched-paired test), and decreased at H4 (23.6 ± 10 pg/ml). IL-6 and IL-8 levels peaked at 4 and 2 hours, respectively, after the onset of CPB. By contrast with the strong positive correlation observed between plasma IL-6 and IL-8 concentrations ( rho = 0.91; p = 0.02, Spearman rank order test), the level of IL-10 production was unrelated to the levels of IL-8 and IL-6.
Our results show that CPB causes the rapid and transient release of IL-10. The differences in kinetics and levels of production between IL-10 and IL-6 and IL-8 suggest different immunoregulatory mechanisms involved in their secretions. The in vivo kinetics of IL-10 during CPB are similar to those observed in experimental murine endotoxemia after lipopolysaccharide challenge. 4 These kinetics contrast with in vitro data showing that IL-10 is produced rather late after lipopolysaccharide stimulation of human monocytes 5 and suggest that other cells could be involved in the release of IL-10 in vivo. The cellular source(s) of IL-10 and the nature of stimuli leading to IL-10 release remain to be determined. We concluded that CPB induced an early IL-10 secretion. Further studies are required to determine whether this IL-10 release plays a beneficial role, by reducing the ischemia-reperfusion inflammatory response, or a detrimental role, by decreasing the cellular immune response.
References
-
Butler J, Rocker GM, Westaby S. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 1993;55:552-9.[Abstract]
-
Frering B, Philip I, Dehoux M, Rolland C, Langlois JM, Desmonts JM. Circulating cytokines in patients undergoing normothermic cardiopulmonary bypass. J THORAC CARDIOVASC SURG 1994;108:636-41.[Abstract/Free Full Text]
-
Wang P, Wu P, Anthes JC, Siegel MI, Egan RW, Billah MM. Interleukin-10 inhibits interleukin-8 production in human neutrophils. Blood 1994;83:2678-83.[Abstract/Free Full Text]
-
Marchant A, Bruyns C, Vandenabeele P, et al. Interleukin-10 controls interferon-
and tumor necrosis factor production during experimental endotoxemia. Eur J Immunol 1994;24:1167-71.[Medline]
-
de Waal Malefyt R, Abrams J, Benett B, Figdor CG, de Vries JE. Interleukin-10 inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 1991;174:1209-20[Abstract/Free Full Text]
