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Inter-individual differences in cytokine release in patients undergoing cardiac surgery with cardiopulmonary bypass
A Roth-Isigkeit1, L Hasselbach, E Ocklitz
1Department of Anaesthesia, Medical University of Luebeck, Luebeck, Germany. isigkeit@medinf.mu-luebeck.de
Insights
Coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) triggers varied cytokine responses. Genetic factors, specifically TNF-alpha and BAT2 polymorphisms, may influence these inflammatory reactions in patients undergoing CABG.
Area of Science:
- Cardiovascular Surgery
- Immunology
- Genetics
Background:
- Cardiac surgery using cardiopulmonary bypass (CPB) induces a systemic inflammatory response characterized by cytokine release (e.g., IL-6, TNF-alpha, IL-1 beta, sIL-2R).
- Understanding patient-specific inflammatory responses is crucial for managing outcomes after coronary artery bypass grafting (CABG).
Purpose of the Study:
- To investigate in vitro and in vivo cytokine responses and white blood cell counts (WBC) in patients with high versus low cytokine secretion post-CABG.
- To explore the role of genetic polymorphisms in TNF-alpha and IL-6 genes, as well as BAT2 and TNF-beta, in modulating cytokine levels during surgical stress.
Main Methods:
- Enrolled twenty male patients undergoing elective CABG with CPB.
- Measured serum cytokine levels (IL-6, TNF-alpha, IL-1 beta, sIL-2R) and WBC counts postoperatively.
- Analyzed genetic polymorphisms in promoter regions of TNF-alpha and IL-6, and BAT2 and TNF-beta intron polymorphisms.
Main Results:
- Patients with high postoperative IL-6 levels exhibited significantly higher TNF-alpha and IL-1 beta levels.
- Inter-individual differences in IL-6 release correlated with variations in other cytokines (TNF-alpha, IL-1 beta, sIL-2R).
- Preliminary data suggest specific genetic profiles (BAT2 allele set 140/150 and TNF-alpha -308 G allele) may be associated with a less sensitive inflammatory response.
Conclusions:
- Cytokine release in the postoperative period following CABG is closely interrelated.
- Significant inter-individual variability exists in cytokine release patterns among patients undergoing CABG with CPB.
- Genetic factors may play a role in determining the extent of the inflammatory response to CABG surgery.
Abstract:
Cardiac surgery with cardiopulmonary bypass (CPB) leads to a systemic inflammatory response with secretion of cytokines (e.g. IL-6, TNF-alpha, IL-1 beta and sIL-2R). The objective of the following study was to investigate in vitro and in vivo cytokine responses and white blood cell counts (WBC) of patients with high versus low cytokine secretion after a coronary artery bypass grafting (CABG) procedure. Twenty male patients undergoing elective CABG surgery with CPB under general anaesthesia were enrolled in the study. On the day of surgery (postoperatively), serum levels of TNF-alpha and IL-1 beta were significantly higher in patients of the high IL-6 level group compared to the respective values in the patient group with low IL-6 levels. The inter-individual differences in IL-6 release in patients undergoing CABG surgery with CPB were accompanied by differences in the release of other cytokines, such as TNF-alpha, IL-1 beta and sIL-2R. To understand whether genetic background plays a role in influencing cytokine plasma levels under surgical stress, we examined the distribution of polymorphic elements within the promoter regions of the TNF-alpha and IL-6 genes, and determined their genotype regarding the BAT2 gene and TNF-beta intron polymorphisms. Our preliminary data suggests that regulatory polymorphisms in or near the TNF locus, more precisely the allele set 140/150 of the BAT2 microsatellite marker combined with the G allele at -308 of the TNF-alpha gene, could be one of the genetic constructions providing for a less sensitive response to various stimuli. Our results suggest: (1) close relationships between cytokine release in the postoperative period, and (2) inter-individually varying patterns of cytokine release in patients undergoing CABG surgery with CPB.