ABSTRACT
Evidence from several lines of investigations suggests that Toll-like receptor 4 [TLR4] is involved in atherosclerosis as a bridge between innate and acquired immunity. Percutaneous coronary intervention [PCI] can trigger inflammation through activation of human TLR4 [hTLR4] on monocytes. Hydrocortisone as an anti-inflammatory and immuno-suppressant agent has multiple mechanisms of action. In this study, we aimed at assessing the effects of hydrocortisone on monocyte expression and activity of hTLR4 in patients underwent PCI. Blood samples were taken from a total of 71 patients with chronic stable angina who were scheduled for a PCI, before the intervention. Thirty patients received 100 mg hydrocortisone prior to the procedure. Control group was composed of 41 patients underwent PCI without receiving hydrocortisone. Blood collection was repeated 2 and 4 h after PCI. The expression of hTLR4 on the surface of CD14[+] monocytes and the serum levels of TNF- alpha and IL-1 beta were measured using flowcytometry and Sandwich ELISA. Compared with controls, hydrocortisone significantly reduced monocyte expression of hTLR4 in test group [P<0.01]. In addition, it had a significant effect on reduction of serum concentrations of TNF- alpha and IL-1 beta in test group in a time-dependent manner [P<0.01]. In this study, hydrocortisone was able to reduce the hTLR4/CD14 positive monocytes and its related pro-inflammatory cytokines, thus it can decrease inflammatory responses following PCI
ABSTRACT
Toll like receptors [TLRs] are well recognized players in inflammatory conditions. Among them TLR-4 is involved in chronic inflammatory processes such as formation of atherosclerotic plaques. The present study was aimed to examine the effects of percutanoeus coronary intervention [PCI] as a revascularization method on monocyte expression of hTLR-4 and on the serum levels of two proinflammatory cytokines [TNF-alpha and IL-1beta]. Blood samples were obtained from 41 patients with stable angina who were candidates for PCI. The samples were collected immediately before and 2h and 4h after PCI. The expression of hTLR-4 on CD14[+] monocytes and the serum levels of TNF-alpha and IL-1beta were measured using flowcytometry and ELISA techniques, respectively. By comparing the frequency of circulating hTLR-4[+]/CD14[+] monocytes at different time points, it was observed that PCI procedure up regulates the monocyte expression of hTLR-4 [p<0.05]. The increase in expression was associated with the elevation of the serum levels of proinflammatory cytokines [p<0.05]. There was a significant correlation between monocyte expression of hTLR-4 and serum levels of TNF-alpha and IL-1beta only before PCI. In spite of parallel increase in the serum levels of proinflammatory cytokines and the monocyte expression of hTLR-4, the correlation did not attain a significant level after PCI intervals. PCI is positively associated with an increase in the monocyte expression of hTLR-4. It is also associated with the elevation in the serum levels of proinflmmatory cytokines. These findings suggest that hTLR-4 monocyte expression may be used as a potential prognostic tool in patients with stable angina undergoing PCI.