The role of single nucleotide polymorphism of IL-6 and IL-10 cytokine on pain severity and pain relief after radiotherapy in multiple myeloma patients with painful bone destructions

摘要

Multiple myeloma (MM) cells interact with bone marrow stromal cells stimulating transcription and secretion of cytokines like IL-6 and IL-10, which are implicated in the progression and dissemination of MM. Regulation of cytokines secretion is under genetic control through genetic polymorphisms in their coding and promoter sequences. It seems that single nucleotide polymorphism (SNP) in the promoter region of various genes may regulate the plasma concentrations of cytokines. Cytokines could be also hypothesized to function as pain modulators as peripheral nociceptors are sensitized by cytokines. The aim was to determine if the SNP of IL-6 and IL-10 cytokines could influence the analgesic response of radiotherapy in the treatment of painful bone destructions in MM patients. 30 patients (19 women and 11 men, median age: 67 years) with MM and painful bone destructions were treated with palliative radiotherapy. Pain was evaluated according to the visual analogue scale and analgesics intake. Pain scores and analgesics use were measured prior to radiotherapy as well as 4, 12 and 24 weeks afterward. Opioid analgesics were converted to the morphine-equivalent daily dose (MEDD). Genomic DNA was extracted from peripheral blood leukocytes and IL-6 and IL-10 gene promoter polymorphisms were analysed with polymerase chain reaction. 60% of patients reported severe pain prior to radiotherapy, which decreased to 13% at the first follow-up visit (p 0.001). The MEDD on admission to the hospital was 75 mg/day which decreased to 46 mg/day at the first follow-up visit (p = 0.033). A significant parameter in pain relief was: age 65 years (p=0.029). We analysed 6 SNPs in the gene promoter region of IL-6 (-597 G/A, -572 G/C, -174 G/C) and IL-10 (-592 A/C, -819 C/T, -1082 A/G) as well as their relation with pain severity and analgesic consumption. Patients who are IL-10 -1082 A/G carriers are prone to respond better to radiotherapy than other patients (p0.05). A borderline association was noted for patients who are IL-6 -597 A/A and G/G carriers - assumed to be at higher risk for severe pain prior to radiotherapy (p=0.07) while for patients who are IL-10 - 1082 A/A carries: the median pain score decreased faster (p=0.08). Patients with genotypes IL-6 -597 A/A and IL-6 -174 C/C required a smaller dose of opioids (p=0.06). SNP of IL-6 and IL-10 cytokines can influence the analgesic response of radiotherapy. Patients with genotype IL-10 -1082 A/G respond better to radiotherapy.