Evaluation of Corticosteroid in Systemic Inflammatory Response Syndrome
Condition: Systemic Inflammatory Response Syndrome
MeSH terms: Syndrome; Systemic Inflammatory Response Syndrome
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): solumedrol; Dexamethasone phosphate
Intervention type(s): Drug; Drug
Intervention description(s): intravenous solution for injection; intravenous solution for injection
Other intervention name(s): methylprednisolone; dexamethasone
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Dexamethasone 21-phosphate; BB 1101
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: SIRS; MiRNA-155; Treg