Increase in plasma and surface CD163 levels in patients undergoing coronary artery bypass graft surgery.

Although haptoglobin polymorphism has been shown to be a genetic risk factor in coronary artery disease, its mechanisms of action are incompletely defined. Recently, a macrophage scavenger receptor for the uptake of haptoglobin-hemoglobin (Hp-Hb) complexes was cloned and designated CD163. Macrophage expression of CD163 is increased by glucocorticoids, IL-10 and IL-6. To better understand the in vivo response of CD163 to an inflammatory stimulus and glucocorticoid treatment, we studied 18 patients who underwent elective coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB). We report a rapid increase in plasma levels of soluble CD163 by 1 h post-declamping the aorta during CABG surgery with CPB. Furthermore, we demonstrate significant increases in monocyte CD163 on post-operative day 1; 14-fold for patients pre-treated with methylprednisolone and 3-fold for those who did not receive exogenous glucocorticoids. These findings show CD163 to be rapidly mobilized in response to systemic inflammatory stimuli and to be affected significantly by glucocorticoids in vivo. The proposed role of CD163 as a Hp-Hb scavenger and anti-inflammatory molecule, in conjunction with the results of this study, make CD163 an intriguing target for potential manipulation of the acute response to inflammation.

Decreased physiologic variability as a generalized response to human endotoxemia.

OBJECTIVE: To test the effect in normal human volunteers of transient systemic inflammation on the variability in time-series behaviors of widely divergent physiologic measures of the human inflammatory response. DESIGN: Prospective study of human volunteers who were tested on 2 consecutive days, a control day and a treatment day. Each participant served as his or her own control. SETTING: Critical care facility of a university medical center. SUBJECTS: Subjects were eight healthy human volunteers. INTERVENTIONS: Participant subjects were tested on both a baseline day with no intervention and on a treatment day when they received 4 ng/kg intravenous Escherichia coli endotoxin. MEASUREMENTS AND MAIN RESULTS: Continuous electrocardiographic recordings and serial blood sampling (performed every 5 mins) were used to create time-series of heart rate (R-R intervals), neutrophil function (phagocytosis), and plasma cortisol concentrations. For each primary measure, we recorded a significant increase in the regularity (decreased variability) of the functional measurement as assessed by the statistical entity, approximate entropy. CONCLUSIONS: Increased regularity, or decreased variability, of organ functions is a generalized response to systemic inflammation that occurs in widely divergent systems during endotoxemia.

Effect of medium tonicity and dextran on neutrophil function in vitro.

BACKGROUND: Multiple investigations have demonstrated that hypertonic saline (HS) diminishes the response of polymorphonuclear leukocytes (PMNs) to stimulation. Recent meta-analysis suggests that hypertonic saline in dextran (HSD) is clinically superior to HS. No work to date has examined the effect of added dextran on this immunomodulatory property. METHODS: Human PMNs were exposed to media of varying osmolarity (220-360 mOsm/L) and stimulated with f-met-leu-phe with or without dextran present in the medium. Cell volume, respiratory burst, PMN aggregation, and beta(2)-integrin (CD18) expression were measured. RESULTS: Stimulation with f-met-leu-phe increased cell volume, respiratory burst, aggregation, and CD18 expression. The increases in cell volume, respiratory burst, and aggregation were significantly attenuated by exposure to hypertonic medium. The addition of dextran to the media did not change the results. CONCLUSION: The alterations in PMN function associated with HS are not changed or attenuated by the addition of dextran, suggesting that the clinically superior HSD may have effects similar to HS in mitigating the tissue damage associated with activated PMNs.