Background: Immunosenescence contributes to reduced vaccine response in elderly persons, and is worsened by deficiencies in nutrients such as Vitamin (Vit-D). The immune system is a well-known target of Vit-D, which can both potentiate the innate immune response and inhibit the adaptive system, and so modulate vaccination response.Objective: This randomized placebo-controlled double-blind trial investigated whether Vit-D supplementation in deficient elderly persons could improve influenza seroprotection and immune response.Design: Deficient volunteers (Vit-D serum <30 ng/mL) were assigned (V1) to receive either 100,000 IU/15 days of cholecalciferol (D, n = 19), or a placebo (P, n = 19), over a 3 month period. Influenza vaccination was performed at the end of this period (V2), and the vaccine response was evaluated 28 days later (V3). At each visit, serum cathelicidin, immune response to vaccination, plasma cytokines, lymphocyte phenotyping, and phagocyte ROS production were assessed.Results: Levels of serum 25-(OH)D increased after supplementation (D group, V1 vs. V2: 20.7 ± 5.7 vs. 44.3 ± 8.6 ng/mL, p < 0.001). No difference was observed for serum cathelicidin levels, antibody titers, and ROS production in D vs. P groups at V3. Lower plasma levels of TNFα (p = 0.040) and IL-6 (p = 0.046), and higher ones for TFGβ (p = 0.0028) were observed at V3. The Th1/Th2 ratio was lower in the D group at V2 (D: 0.12 ± 0.05 vs. P: 0.18 ± 0.05, p = 0.039).Conclusions: Vit-D supplementation promotes a higher TGFβ plasma level in response to influenza vaccination without improving antibody production. This supplementation seems to direct the lymphocyte polarization toward a tolerogenic immune response. A deeper characterization of metabolic and molecular pathways of these observations will aid in the understanding of Vit-D's effects on cell-mediated immunity in aging. This clinical trial was registered at clinicaltrials.gov as NCT01893385.

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Thoracotomy is often responsible for chronic pain, possibly of neuropathic origin. To confirm preclinical studies, the preventive effects of perioperative ketamine were tested in a randomized, double-blind, placebo-controlled clinical trial on persistent neuropathic pain after thoracotomy. Eighty-six patients scheduled for thoracotomy under standardised general anaesthesia were randomised to receive either ketamine (1 mg kg(-1) at the induction, 1 mg kg(-1) h(-1) during surgery, then 1 mg kg(-1) during 24 h; n=42) or normal saline (n=44). Postoperative analgesia included a single dose of intrapleural ropivacaine, intravenous paracetamol and nefopam, and patient-controlled intravenous morphine. Vital parameters and analgesia were recorded during the 48 first postoperative hours. Seventy-three patients were followed up. The patient's chest was examined 1-2 weeks, 6 weeks and 4 months after surgery. At the last two observations, spontaneous pain score over a one-week period (visual analogue scale), neuropathic pain score (NPSI), and intake of analgesics, were assessed. No drug affecting neuropathic pain (except opiates) was given during the follow-up. Two patients in each group were lost to follow-up after the 6 week visit. Ketamine improved immediate postoperative pain, but the groups were similar in terms of neuropathic pain and intake of analgesics, 6 weeks (NPSI score: ketamine: 1.25 [0-4.125]; placebo: 1 [0-4]) and 4 months after surgery. Thus, ketamine given in 24-h infusion failed to prevent chronic neuropathic pain after thoracotomy. Other perioperative preventive long-lasting treatments or techniques could be tested in this context.