The early in‐vivo effects of a single anti‐emetic dose of dexamethasone on innate immune cell gene expression and activation in healthy volunteers

Abstract

Dexamethasone is often administered to surgical patients for anti-emetic prophylaxis. This study examined the early (up to 24 h) in-vivo effects of dexamethasone (8 mg) to demonstrate the magnitude and temporal nature of changes on circulating peripheral blood mononuclear cell gene expression and activation in 10 healthy male volunteers. Blood samples were drawn at baseline, 2 h, 4 h and 24 h. Gene expression was measured using quantitative real-time polymerase chain reaction. Cytokine expression was measured using multiplex immuno-assays. Innate immune cell phenotypes were examined with flow cytometry. Dexamethasone resulted in rapid transient changes in immunophilin (p = 0.0247), plasminogen activator inhibitor-1 (p = 0.0004), forkhead box P3 (p = 0.0068) and dual specific phosphatase-1 (p = 0.0157) gene expression at 4 h compared with pre-dexamethasone. Plasma interleukin-10 levels increased within 2 h (p = 0.0071) and returned to baseline at 24 h. Reductions in classical (p = 0.0009) and intermediate monocytes (p = 0.0178) and dendritic cells (p = 0.0012) were followed by increases in the level of these populations at 24 h compared with pre-dexamethasone (classical monocytes p = 0.0073, intermediate monocytes p = 0.0271, dendritic cells p = 0.0142). There was a profound reduction in the mean fluorescence intensity of the maturation marker, human histocompatibility leucocyte antigen, at 24 h in all monocyte subsets (p = 0.0002 for classical and non-classical monocytes, p = 0.0001 for intermediate monocytes) and dendritic cells (p = 0.0001). This study confirms rapid transient effects of 8 mg dexamethasone on innate immune cells with the potential to alter the inflammatory response to surgery and provides support for the hypothesis that intra-operative administration may be both immunosuppressive and immune-activating in the immediate peri-operative period.

Possible dose dependent effect of perioperative dexamethasone and laparoscopic surgery on the postoperative systemic inflammatory response and complications following surgery for colon cancer

“…In relation to the innate immune system, increased transcription of lipocortins leads to down-regulation of cyclo-oxygenase related pathways, whilst steroids decrease circulating pro-inflammatory mediators including IL 6, resulting in an overall lessening of this response [19][20]. Recent evidence in healthy volunteers and surgical patients given doses of dexamethasone similar to that used to prevent PONV have shown rapid effects on circulating innate immune cells and circulating cytokines and may both initially attenuate innate immune responses but then allow for later immune activation, suggesting an immunomodulatory role rather than that of straightforward immunosuppression [21][22].…”

Adverse side‐effects of dexamethasone in surgical patients – an abridged Cochrane systematic review

“…It is known that long‐term treatment with corticosteroids can produce many side‐effects, such as: adrenal insufficiency; increased risk of wound infections; hyperglycaemia; and even development of diabetes mellitus . However, it is unknown whether a single dose of dexamethasone given in the peri‐operative period has the same adverse side‐effects as seen with long‐term treatment .…”

Dexamethasone in regional anaesthesia: travelling up a blind alley?

“…But it is a matter of fact, there is no known inhibitory effect of dexamethasone on conduction in healthy nerves. It remains possible that dexamethasone shows useful effects on nerves affected by local inflammation through modulation of gene expression – similar to the effects of opioids in chronic pain therapy. But this is a completely different story and specific and very well‐designed studies would be required to test this hypothesis.…”