Cyclical ischaemic preconditioning modulates the adaptive immune response in human limb ischaemia–reperfusion injury
- 12 March 2009
- journal article
- research article
- Published by Oxford University Press (OUP) in British Journal of Surgery
- Vol. 96 (4), 381-390
- https://doi.org/10.1002/bjs.6554
Abstract
Background: Reperfusion injury (RI) has significant local and systemic consequences. Ischaemic preconditioning (IPC) modulates RI and the innate immune response. This study examined whether IPC attenuates RI-mediated changes in lymphocyte populations and function following elective surgery.Methods: Twenty-five patients sustaining 1 h of tourniquet ischaemia during cruciate ligament reconstruction were randomized before surgery to three 5-min ischaemia cycles separated by 5 min of reperfusion, or to a control group. Systemic levels of interleukin (IL) 4 and interferon (IFN) γ, and surface expression of CD45ro/ra, CD62L and CD95 were measured. T cells were examined systemically and in stimulated serum co-culture to determine CD4/CD8 and Th1/Th2 shifts through intracellular cytokine production.Results: CD4 CD45ro cell numbers increased after RI without IPC, whereas CD8 cells expressing CD45ro and CD95 increased with IPC. Preconditioned serum in co-culture attenuated increases in CD4 and decreases in CD8 numbers, a process prevented by inhibition of antigen activation. Following RI, systemic IL-2 levels were significantly lower after IPC, whereas co-culture with post-RI serum increased proinflammatory intracellular cytokine production.Conclusion: IPC modulated T cell responses in limb RI through reduced activation and proinflammatory cytokine production by CD4 cells, while preventing CD4/CD8 derangement. IPC prevented lymphocyte-directed immune dysfunction.Keywords
This publication has 37 references indexed in Scilit:
- London's disastrous drug trial has serious side effects for researchNature, 2006
- T cells as mediators in renal ischemia/reperfusion injuryKidney International, 2004
- T-Lymphocytes Modulate the Microvascular and Inflammatory Responses to Intestinal Ischemia-ReperfusionMicrocirculation, 2002
- Caspase inhibition protects from liver injury following ischemia and reperfusion in ratsTransplant International, 2000
- Requirement for interleukin-12 in the pathogenesis of warm hepatic ischemia/reperfusion injury in miceHepatology, 1999
- Interleukins 18 and 12 Synergistically Upregulate Interferon-γ Production by Murine Dendritic Epidermal T CellsJournal of Investigative Dermatology, 1999
- Myocardial adaptation to ischaemia – the preconditioning phenomenonInternational Journal of Cardiology, 1999
- Ischaemia-reperfusion injuryBritish Journal of Surgery, 1994
- Differential Regulation of Murine T Lymphocyte SubsetsAnnual Review of Immunology, 1993
- CD4+ T-cell subsets: regulation of differentiation and functionResearch in Immunology, 1991