Systemic Inflammatory Response Syndrome
Conditions
Keywords
SIRS, MiRNA-155, Treg
Brief summary
Cardiac surgery and cardiopulmonary bypass (CPB) initiate a whole-body systemic inflammatory response (SIRS) characterized by the activation of leukocytes, monocytes, and the complement cascade. Multiple mediators of the inflammatory process are released, including cytokines, endothelin, adhesion molecules, and oxygen free radicals. An exaggerated release of these mediators may contribute to numerous postoperative end-organ complications, including myocardial dysfunction, neurologic impairment, respiratory failure, altered renal and hepatic function, bleeding disorders, and multiple organ failure. Although most cardiac surgical patients do not experience major adverse events, it is likely that the inflammatory response impairs clinical recovery to some degree in all patients. A large number of therapeutic strategies have been developed to attenuate the inflammatory reaction to CPB and thereby enhance recovery of the cardiac surgical patient. Intraoperative corticosteroid administration has been studied extensively as a primary pharmacologic anti-inflammatory treatment option.
Detailed description
Investigations have shown that clinical outcomes have been improved, worsened, or unaffected by the intraoperative administration of dexamethasone or methylprednisolone Limited data suggest that low-dose corticosteroids may be as effective as high-dose treatment in reducing complications but with fewer potential side effects MicroRNAs (miRNAs) are protein regulators that play an important role in a wide range of cellular functions. There is increasing evidence for the close relationship between miRNA expression, Th17 cell differentiation and disease pathology The miRNA, miR-155, which was the subject of this study, has a range of known biological functions, which include the induction of Toll like receptor (TLR) activation in monocytes /macrophages and the modulation of TLR signaling, facilitating pro-inflammatory cellular responses and initiating systemic inflammatory responses, as well as regulating Treg cell differentiation, maintenance, and function. The expression of this miRNA can be induced by inflammatory cytokines, such as tumor necrosis factor α (TNFα), that are released into the circulation in the initial stages of a systemic inflammatory response. In another study, demonstrated that miR-155 enhanced Treg and Th17 cell differentiation and Th17 cell function by targeting (suppressor of cytokine signaling 1) SOCS1. In this study, the investigators will compare effect of low dose intra-operative corticosteroid (dexamethasone and methylprednisolone) as anti-inflammatory modulators through detection of T regulatory cells(Tregs) and IL-17 and correlate relation between Treg, IL-17 and micro RNA-155.
Interventions
intravenous solution for injection
intravenous solution for injection
Sponsors
Study design
Eligibility
Inclusion criteria
* open heart surgery with Cardiopulmonary bypass machine with relatively long bypass time more than 60 minute * All patients Included in study with normal heart function
Exclusion criteria
* Left ventricular ejection fraction less than 40% * acute infection such as sepsis or pneumonia, hepatic and renal failure, cancer or any autoimmune disease * the use of steroid within 2 week prior to operation * coagulation abnormalities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| measure anti-inflammatory effect through detection T regulatory cell level by4 color flow cytometry analysis to quantify % of Tregs (CD4, CD25,FoxP3) | 72 hours post operative | in blood of all subjects |
| detect microRNA-155 | 72 hours post operative | micro-RNA 155 is measured by RT-PCR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| measure pro-inflammatory cytokines | 72 hours post operative | pro-inflammatory cytokines such as IL-1 and IL-6 by ELISA. |
Countries
Egypt