Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 36, Issue 8, Pages 1434-1448Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X15620204
Keywords
Chemokines; brain trauma; microglia; inflammation; neurochemistry
Categories
Funding
- joint Medical Research Council/Royal College of Surgeons of England Clinical Research Training Fellowship [G0802251]
- Raymond and Beverly Sackler Fellowships
- Royal College of Surgeons of England Research Fellowship
- National Institute for Health Research Biomedical Research Centre, Cambridge (Neuroscience Theme
- Brain Injury and Repair Theme)
- National Institute for Health Research Senior Investigator Awards
- Academy of Medical Sciences/Health Foundation Senior Surgical Scientist Fellowship
- National Institute for Health Research Brain Repair Centre Collaborative
- National Institute for Health Research Professorship
- Medical Research Council [G0600986, 79068]
- MRC [G9439390, G1002277, G0802251, G0600986, G0601025] Funding Source: UKRI
- Medical Research Council [G0601025, G0600986, G0001354, G1000183B, G0802251, G9439390, G0001354B, G1002277] Funding Source: researchfish
- National Institute for Health Research [NIHR-RP-R3-12-013, ACF-2006-14-004, NF-SI-0512-10090, NF-SI-0508-10327] Funding Source: researchfish
Ask authors/readers for more resources
Interleukin-1 receptor antagonist (IL1ra) has demonstrated efficacy in a wide range of animal models of neuronal injury. We have previously published a randomised controlled study of IL1ra in human severe TBI, with concomitant microdialysis and plasma sampling of 42 cytokines and chemokines. In this study, we have used partial least squares discriminant analysis to model the effects of drug administration and time following injury on the cytokine milieu within the injured brain. We demonstrate that treatment with rhIL1ra causes a brain-specific modification of the cytokine and chemokine response to injury, particularly in samples from the first 48 h following injury. The magnitude of this response is dependent on the concentration of IL1ra achieved in the brain extracellular space. Chemokines related to recruitment of macrophages from the plasma compartment (MCP-1) and biasing towards a M1 microglial phenotype (GM-CSF, IL1) are increased in patient samples in the rhIL1ra-treated patients. In control patients, cytokines and chemokines biased to a M2 microglia phenotype (IL4, IL10, MDC) are relatively increased. This pattern of response suggests that a simple classification of IL1ra as an 'anti-inflammatory' cytokine may not be appropriate and highlights the importance of the microglial response to injury.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available