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.

Crohn's disease affects increasing numbers of children worldwide. Generally, childhood-onset disease runs a more severe course than in adults and has a greater impact on quality of life. Therapy in children must take account of a different set of risks for toxicity compared to adults, but also to their longevity. Biologic drugs present remarkable advantages in terms of disease control for children, especially in those whose disease cannot be controlled with conventional therapies, but their long-term risks are still being assessed. Data regarding biologic use in children is limited and mostly amounts to case series, but results have been promising, both in terms of controlling disease activity and improving growth parameters. Adverse reactions are infrequent in the short term, but loss of response is a long-term problem, particularly in children. More information is needed about very long term risks. Infliximab and adalimumab are the most studied agents in children, while there is relatively limited data on certolizumab and natalizumab. Further collection of data on these agents is still needed, but this should not restrict access to these agents for children in whom no other agent is effective.

Secondary loss of response (LoR) often precludes further use of infliximab in children with Crohn’s disease. Immunomodulators may reduce the incidence of LoR but their combination with infliximab presents safety concerns. We aimed to determine the long-term durability of infliximab response in paediatric Crohn’s, effect of immunomodulators on LoR, and secondarily the effect of infliximab on growth. We retrospectively audited patients on maintenance infliximab at a single centre. Data included height and weight, Paediatric Crohn’s Disease Activity Index (PCDAI), and immunomodulator use. 71 children (32% female, mean age 14.4 years) had been commenced on maintenance infliximab before July 2011. 89% had been on immunomodulators concurrently with infliximab. LoR occurred in 20 (28%), with a median time to LoR of 4.31 years. LoR was significantly increased in children who did not enter remission (PCDAI ≤ 10) after induction (p < 0.05). LoR occurred more frequently in the 72% who ceased immunomodulators, but this failed to reach statistical significance (p = 0.300). Height and weight SDS improved significantly on infliximab. Infliximab is a durable long-term therapy for paediatric Crohn’s refractory to conventional therapy. A large-magnitude increase in the rate of loss of response after immunomodulator cessation was not observed.

Dexamethasone is frequently administered to surgical patients for anti-emetic prophylaxis. We have examined the immunomodulatory effects of a single bolus of dexamethasone on circulating peripheral blood mononuclear cells (PBMCs) in the same 10 healthy male volunteers, previously used in our investigation on early in vivo effects of a single anti-emetic dose of dexamethasone on innate immune cell gene expression and activation [1] . Blood samples were drawn at baseline, 2 h, 4 h and 24 h. Immune cell phenotypes were examined with flow cytometry. In this data article the expression strength of markers involved in immune activation and immunosuppression as well as maturation, migration, cell death and responsiveness to signalling on monocyte and cDC subsets, as well as NK cells, CD4+ and CD8+ T cells and regulatory T cells (Treg) are presented. These data improve our understanding of the immunomodulatory effects of the glucocorticoid dexamethasone in-vivo , which may be important for the optimisation of treatment regimens as well as the evaluation of new indications for glucocorticoid treatment.