Bedeutung von Cannabis für die Trauma-induzierte inflammatorische Immunantwort unter Berücksichtigung des A118G Polymorphismus im µ-Opioidrezeptor

Abstract

The systemic inflammatory response syndrome (SIRS) induced by major surgical trauma is often followed by immunosuppression and increased susceptibility to postoperative infections and sepsis. Additional suppressive effects caused by pain therapy with opioids may differ in individual patients due to µ-opioid receptor (µOPR) single nucleotide polymorphism (SNP) at position A118G, studied here. We also analyzed changes induced by partial substitution of the µ-opioid induced analgesia by Cannabis (delta9-Tetrahydrocannabinol, THC). Eighty-three patients with prostate carcinoma underwent radical prostatectomy and received the opioid Piritramide. Before and till day+2 post surgery 43 patients received a partial substitution by the cannabinoid Dronabinol (40mg in total) as placebo-controlled trial. Patients’ plasma samples were tested for cytokines and metalloproteinases (MMP) by Luminex Multiplex Assays before (day0) and on the first and second postoperative day (day+1, day+2). DNA was analysed for the µOPR SNP A118G genotype by allele-specific pyrosequencing using a PSQ TM 96 MA (Biotage). We defined six groups regarding THC test (positive/ negative) and genotype for µOPR SNP A118G (wildtype/ heterozygous/ homozygous mutated genotype). On day+1 post surgery plasma concentrations for TNF-alpha, Interleukin 1beta, MMP-1, MMP-9 and MMP-13 were found to be significantly higher in patients w/o THC medication (p < 0.05) independently of their µOPR genotype. By contrast, the levels of anti-inflammatory IL-10 and IL-13 did not differ in THC positive and negative patients. No difference in cytokine and MMP distribution could be observed in patients with different genotype for the SNP A118G. We conclude that perioperative administration of THC combined with µ-opioid analgesics attenuated the inflammatory Th1 response, independently of the µOPR SNP A118G genotype. The use of Cannabis as additive in perioperative pain therapy may therefore prevent hypercytokinemia induced by trauma.