Aim and methods: To investigate the safety, tolerability, pharmacodynamics and pharmacokinetics of the adrenomedullin-binding antibody Adrecizumab during experimental human endotoxemia in a randomized, double-blind, placebo-controlled manner in 24 healthy human volunteers.
Conclusion: Administration of Adrecizumab was safe and well tolerated in the presence of systemic inflammation. These findings pave the way for further investigation of Adrecizumab in sepsis patients.
Link: https://www.ncbi.nlm.nih.gov/pubmed/29856470
Aim and methods: To investigate immunostimulatory effects of acetylsalicylic acid (aspirin) during systemic inflammation and endotoxin tolerance. Healthy volunteers were randomized to receive either 80mg acetylsalicylic acid or placebo and subsequently challenged with endotoxin twice, at a 1-week interval.
Conclusion: Treatment with low-dose acetylsalicylicacid partially reverses endotoxin tolerance in humans in vivo by shifting response toward a proinflammatory phenotype.
Link: https://journals.lww.com/ccmjournal/Abstract/onlinefirst/Treatment_With_Acetylsalicylic_Acid_Reverses.96065.aspx
Aim and methods: In vitro and animal studies have shown different, opposing effects of hypoxia on the innate immune response. Meanwhile, there is a trend towards more conservative oxygen strategies in patients in the Emergency Department and Intensive Care Unit with acute inflammatory diseases such as sepsis. We studied the effect of short term hypoxia (SpO2 80-85% for 3.5 hours) on the cytokine response after endotoxin administration in healthy subjects.
Conclusion: Short term hypoxia results in a strong, early augmentation of the anti-inflammatory interleukin-10 and a subsequent attenuation of pro-inflammatory cytokines.
Link: https://www.ebiomedicine.com/article/S2352-3964(18)30228-7/abstract
Aim and methods: In post-hoc analysis from randomized controlled trials, sepsis-related mortality appears to be lower in post-myocardial infarction patients treated with ticagrelor when compared to those treated with clopidogrel. We investigated whether ticagrelor, when compared to clopidogrel, both in combination with acetylsalicylic acid, has immunomodulating effects that may explain these differences. Healthy volunteers were treated with placebo, monotherapy acetylsalicylic acid, ticagrelor-acetylsalicylic acid or clopidogrel-acetylsalicylic acid. At day 7 a cytokine response was induced by endotoxin administraton.
Conclusion: Monotherapy acetylsalicylic acid augmented the pro-inflammatory cytokine response compared to placebo. There was no relevant effect on the cytokine response of neither ticagrelor nor clopidogrel.
Link: https://www.thieme-connect.com/products/ejournals/abstract/10.1160/TH16-10-0799
Aim and methods: To ascertain the effects of vasopressors on the innate immune response in vivo, 40 healthy male volunteers were randomized to receive a 5-hour infusion of either noradrenaline (0.05µg/kg/min), phenylephrine (0.5µg/kg/min), vasopressin (0.04 IU/min) or placebo (NaCl 0.9%) in a double blinded manner. 1 hour after the start of the vasopressor infusion they were given an LPS bolus (2ng/kg) to elicit a systemic inflammatory response.
Conclusion: Both noradrenaline and phenylephrine induced significantly higher circulating levels of the anti-inflammatory cytokine IL-10, and significantly lower levels of pro-inflammatory chemokines MIP-1β and CXCL-10, compared to placebo. Vasopressin did not significantly influence the cytokine levels in this trial, compared to placebo. Noradrenaline and phenylephrine shift the balance towards an anti-inflammatory phenotype during human experimental endotoxemia in vivo.
Link: https://www.atsjournals.org/doi/full/10.1164/rccm.201604-0862CP
Welcome to Radboudumc How can we help you?
See the overview of studies (mostly "trials") in which you can participate as a healthy person or as a patient with a disorder.
Please note that more studies may be available for participation, but only in Dutch.
Studies for which registration has already closed or which have been fully completed but are still available for viewing can be found here.
NL
DE
