Modulation of the cellular and humoral immune response to pediatric open heart surgery by methylprednisolone

Abstract

Background: With the intention to reduce overshooting immune response, glucocorticoids are frequently administered perioperatively in children undergoing open heart surgery. In a retrospective study we investigated extensively the modulation of the humoral and cellular immune response by methylprednisolone (MP).Methods: This study was carried out on blood samples from two groups of children who had undergone surgical correction of atrial or ventricular septal defects, either without (MP 2 , n 5 10), or with MP administration (MP 1 , n 5 23, dose median 11 (IQR 10-16) mg kg 21 body weight) before cardiopulmonary bypass (CPB, duration median 42 (IQR 36-65) min). EDTA blood was obtained 24 h preoperatively, after anesthesia, at CPB begin and end, 4, 24, and 48 h after surgery, at discharge and at out-patient follow-up (median 8.2 (IQR 3.3-12.2) months after surgery). Complex blood analysis including clinical chemistry and flow cytometry were performed to monitor humoral immune response, differential blood count, lymphocyte subsets, and the degree of activation of various leukocyte subpopulations.Results: The patients' postoperative courses and follow-up were uneventful. Release of IL-6 and IL8 was reduced and that of the anti-inflammatory cytokine IL-10 upregulated by MP. Significant increase of circulating neutrophils and monocytes as inflammatory reaction to surgery and CPB contact was detected in both groups. However, invasion of monocytes to the periphery was delayed with MP. CD41 and CD81 T-lymphocyte counts were lower with MP treatment. B-lymphocyte count increased significantly after surgery in MP 1 but remained constant in MP 2 group. Conclusions: MP treatment partially decreased the pro-inflammatory effect of CPB surgery and induced anti-inflammatory effect on the cellular and humoral level.

Clinical recovery from surgery correlates with single-cell immune signatures

“…S2, 3). Consistent with previous reports (11, 13, 15, 16, 34), surgery induced a 1.2-fold (±0.06, q<0.01) expansion of neutrophils 1 h after surgery, a 1.9-fold (±0.19, q<0.01) expansion of CD14 + MCs at 24 h, and a contraction of CD4 + and CD8 + T cells to 0.77-fold (±0.07, q<0.01) and 0.71-fold (±0.07, q<0.01), respectively, at 24 h (Fig. S3).…”

“…Consistent with previous studies (11, 13–15, 34, 47), innate immune cells expanded soon after surgery, followed by a reduction of cells within the adaptive branch (Fig. 3).…”

“…Traumatic injury initiates an intricate programmed immune response (9): Hours following severe trauma, neutrophils and monocytes are rapidly activated and recruited to the periphery by damage-response antigens, alarmins (e.g., HMGB1), and increased levels of TNFα, IL-1β, IL-6 (10–13). This is followed by a compensatory phase characterized by decreased numbers of T cell subsets (13–16).…”

“…This is followed by a compensatory phase characterized by decreased numbers of T cell subsets (13–16). The various immune cell types are thought to integrate multiple environmental signals into cohesive signaling responses that enable wound healing and recovery.…”

Steroids in paediatric heart surgery: eminence or evidence-based practice?

“…Some studies found that steroids can blunt inflammation [7][8][9][10][11][12][13][14] while others found the opposite [15]. Most importantly, it is unclear to what degree this presumed Banti-inflammatoryê ffect also translates into better clinical outcomes [7,10,13].…”