Alteration of cytokine profile following hemorrhagic shock

Abstract

Hemorrhage is one of the leading causes of death in patients with trauma. We recently demonstrated that resveratrol can improve cardiac function and prolong life following severe hemorrhagic injury (HI) in a rat model. The present work is focused on determining changes in NF-κb dependent gene expression in the heart and the systemic cytokine milieu following HI and the effect of resveratrol treatment. The results indicate an increase in phosphorylated NF-κb in the heart with a concomitant increase in the expression of NF-κb dependent genes following HI. There was also a significant increase of systemic cytokine levels, both pro and anti-inflammatory, following HI and resolution when treated with resveratrol. This study demonstrates the potential role NF-κb has in the physiological response to HI and the effectiveness of resveratrol in reducing immune activation.

Mitochondrial dysfunction in rat splenocytes following hemorrhagic shock

“…The increased expression of HMGB1 in splenocytes is consistent with the systemic inflammatory response observed following HI. Our lab and others have reported the increased level of plasma cytokines immediately after HI (34, 49). Some of these cytokines begin to appear as early as one hour after HI (34, 38, 50, 51).…”

“…Our lab and others have reported the increased level of plasma cytokines immediately after HI (34, 49). Some of these cytokines begin to appear as early as one hour after HI (34, 38, 50, 51). The initial inflammatory response is likely to be a repair process to balance cellular homeostasis, but persistent exacerbated inflammation following the initial insult contributes to organ dysfunction (5, 52, 53).…”

“…Our experiments using snap frozen spleens show a significantly increased expression of several cytokines including IL-6. Consistent with these gene expression changes, the expression of the p65 subunit of inflammation promoting transcription factor NF-kb was also significantly increased (34, 56–58). The observation of an active immune response in the spleen needs to be further characterized by phenotyping splenocyte subsets and correlating with intracellular cytokine expression.…”

“…A systemic inflammatory response as evidenced by an increase in the levels of pro- and anti-inflammatory cytokines is a hallmark of HI (33). Our recent studies demonstrated a significant increase in the plasma levels of cytokines such as IL-6, TNF-α and IL-10 and activation of NF-κb (34). The hypoxic response of the host is complex as reduced oxygen availability can lead to altered mitochondrial energy metabolism as well as an inflammatory trigger (35, 36).…”

The grapes and wrath: using resveratrol to treat the pathophysiology of hemorrhagic shock

“…In several rodent models of HSR, the cellular benefits of resveratrol clearly correlate with improved organ function up to 24 h postshock. When given during resuscitation, resveratrol decreased the expression of circulating inflammatory mediators and downregulated the expression of cytokines, chemokines, and adhesion molecules in multiple organs, including the liver, lung, intestine, and heart . Importantly, the decrease in proinflammatory mediators correlated with fewer neutrophils migrating into tissues and decreased tissue damage .…”