Desensitization of the inflammatory response in humans: changes in response to cardiopulmonary bypass.
Although circulating levels of interleukin 8 (IL-8), a potent pro-inflammatory chemokine, and many other inflammatory mediators increase in response to cardiopulmonary bypass, only a small proportion of patients develop a clinically significant systemic inflammatory response. The natural mechanisms that control the inflammatory response are poorly understood. To investigate the role of IL-8 in a human inflammatory model, 15 adult patients undergoing cardiopulmonary bypass for elective coronary artery bypass grafting were studied. Following reperfusion, plasma IL-8 levels increased significantly from 58 pg/mL (pre-bypass) and 66 pg/mL (after 20 min of bypass) to 98 pg/mL (p = .02 and .04, respectively), but this was accompanied by a concomitant threefold decrease in the IL-8 binding affinity of circulating neutrophils (Dissociation constant (KL) post-reperfusion/KL pre-bypass = 3.2; KL post-reperfusion/KL after 20 min of bypass = 2.8). IL-8-triggered release of myeloperoxidase and elastase by peripheral blood neutrophils ex vivo was also down-regulated following reperfusion. There were no significant changes in beta 2 integrin expression or inositol polyphosphate metabolism of peripheral blood neutrophils. These changes in receptor affinity and neutrophil responsiveness to IL-8 may represent an important in vivo regulatory mechanism which serves to prevent excessive tissue injury from inflammatory triggers.
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T T
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Department of Immunology, St. Bartholomew's, London, United Kingdom.
Gibson
F A
FA
Nye
K E
KE
Hughes
P J
PJ
Hinds
C J
CJ
Morrow
W J
WJ
Ferguson
C
C
D015703:Antigens, CD / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D003432:Cross-Linking Reagents; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D007295:Inositol Phosphates / Q000378:metabolism; D016209:Interleukin-8 / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D019272:Leukocyte Elastase / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D023062:Receptors, Interleukin-8A; D015398:Signal Transduction
D015703:Antigens, CD; D018821:CD18 Antigens; D003432:Cross-Linking Reagents; D007295:Inositol Phosphates; D016209:Interleukin-8; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D009195:Peroxidase; D019272:Leukocyte Elastase