Artikel
Pro-inflammatory TH1-response in SIRS is attenuated by cannabis (delta9-THC) supplemented opioid therapy independently of the MU-opioid receptor (µOPR) Polymorphism A118G
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Autoren
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Lea Fritzenschaft
- Uniklinik Ulm, Klinik für Allgemein- und Viszeralchirurgie, Ulm, Germany
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Knut M. Wittkowski
- The Rockefeller University Hospital, Center for Clinical and Translational Science, New York, United States
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Weidong Du
- Uniklinik Ulm, Klinik für Allgemein- und Viszeralchirurgie, Ulm, Germany
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Manfred Weiss
- Uniklinik Ulm, Sektion Experimentelle Anästhesie, Ulm, Germany
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Thomas O. Joos
- University of Tübingen, NMI Natural and Medical Sciences Institute , Kusterdingen, Germany
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Marion E. Schneider
- Uniklinik Ulm, Sektion Experimentelle Anästhesie, Ulm, Germany
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Peter Steffen
- Uniklinik Ulm, Klinik für Anästhesiologie, Sektion Schmerztherapie, Ulm, Germany
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Stephan Paschke
- Uniklinik Ulm, Klinik für Allgemein- und Viszeralchirurgie, Ulm, Germany
| Veröffentlicht: | 10. Oktober 2016 |
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Gliederung
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Objectives: Major inflammation induced by tissue damage and the release of danger associated molecular patterns (DAMPs) conditions for immune dysfunction against nosocomial and community derived infectious agents. The inflammatory response after surgery may further influenced by perioperative pain therapy. We therefore addressed the influence of opioids and cannabinoids on post operative pain as well as pro-inflammatory cytokines. A crosstalk between the Cannabis and ligands for the µ-opioid receptors has been suggested. We studied changes induced by partial substitution of the µ-opioid induced analgesia by delta9-tetrahydro-cannbinol (delta9THC). While doing this, we considered the µOPR single nucleotide polymorphism (SNP) at position A118G to influence individual patients' opioid response.
Methods: Ninety-three patients with prostate carcinoma underwent radical prostatectomy and received the opioid Piritramide. Before and till day 2 post surgery 49 patients received the cannabinoid delta9-THC (40mg in total) as placebo-controlled trial. Patients' plasma samples were tested for concentrations of cytokines and metalloproteinases (MMP) by Luminex Multiplex Assays. DNA was analyzed for the µOPR SNP A118G by allele-specific pyrosequencing a PSQ 96 MA (Qiagen). We defined six groups regarding delta9-THC test (positive/negative) and genotype for µOPR SNP A118G (wildtype/heterozygous/homozygous mutated genotypes).
Results and Conclusion: On day+1 post surgery, plasma concentrations of pro-inflammatory mediators were found to be higher in patients w/o delta9-THC medication (p < 0.15, Table 1) independently of their OPRM1 genotype. By contrast, the levels of anti-inflammatory IL-10 and IL-13 did not differ in delta9-THC positive and negative patients.
We conclude that perioperative administration of delta9-THC combined with µ-opioid analgesics attenuated the inflammatory Th1 response, independently of the µOPR SNP A118G genotype. The use of Cannabis may therefore prevent immune dysfunction induced by trauma.
