Failure of cell-mediated immunity is thought to increase the morbidity and mortality rates after trauma and major surgical procedures and to be the result, in part, of a redirection of CD4(+) T cells toward T(H2) differentiation. We tested the hypothesis that morphine treatment after injury promotes T(H2) differentiation of precursor T cells through the mu-opioid receptor.
Human peripheral blood mononuclear cells (PBMCs) or splenocytes from either wild type or mu-opioid receptor knock-out mice were treated in vitro with either vehicle or morphine and then stimulated with anti-CD3/anti-CD28. The supernatant was assayed for T(H1) (interleukin-2 [IL-2], interferon gamma [IFN gamma]) and T(H2) (IL-4, IL-5) cytokines (enzyme-linked immunosorbent assay). Morphine regulation of IL-4 transcription was investigated in PBMCs (IL-4 messenger RNA, nuclear factor of activated T-cells) and Jurkat T cells transfected with a murine IL-4 promoter-luciferase construct. Morphine-induced nuclear factor of activated T-cell (NFAT) binding was assayed with the electromobility shift assay in Jurkat T cells.
Morphine treatment of PBMCs decreases IL-2 and IFN gamma and increases IL-4 and IL-5 as a function of morphine concentration. Morphine treatment in wild type splenocytes inhibited IFN gamma and stimulated IL-4 protein synthesis. Changes in cytokine synthesis were abolished in mu-opioid receptor knockout mice. Morphine treatment increases IL-4 messenger RNA accumulation in PBMCs and increases IL-4 promoter activity in Jurkat T cells. Morphine increases NFAT nuclear protein binding to an NFAT DNA response element.
We conclude that morphine treatment promotes T(H2) differentiation through a mu-opioid receptor mechanism and that morphine treatment increases IL-4 transcription, in part, through an NFAT mechanism.
Pharmacology, Toxicology and Pharmaceutical Science
4
10%
Neuroscience
4
10%
Biochemistry, Genetics and Molecular Biology
3
8%
Immunology and Microbiology
3
8%
Other
5
13%
Unknown
12
31%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 March 2016.
All research outputs
#12,064,104
of 33,940,276 outputs
Outputs from Surgery
#4,371
of 9,641 outputs
Outputs of similar age
#25,067
of 58,986 outputs
Outputs of similar age from Surgery
#17
of 30 outputs
Altmetric has tracked 33,940,276 research outputs across all sources so far. This one is in the 38th percentile – i.e., 38% of other outputs scored the same or lower than it.
So far Altmetric has tracked 9,641 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.7. This one is in the 32nd percentile – i.e., 32% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 58,986 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 8th percentile – i.e., 8% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 30 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
