Inflammatory Response to Chronic Opioid Exposure in Humans

Abstract

Abstract Objective In this study, we investigated if chronic opioid exposure leads to changes in immune signaling pathways. Method We used phospho-flow cytometry to study intracellular signaling in immune cells of patients with chronic opioid exposure. PBMCs were stimulated with cytokines (IFN-α, IFN-γ, IL-2, IL-6, IL-7, IL-10, IL-21), then stained to analyze 6 lymphocyte subsets and monocytes for phosphorylated STATs (signal transducers and activators of transcription), in particular p-STATs 1, 3 and 5. Results After one month of opioid exposure as compared to baseline, IL-2 stimulation of B cells resulted in significantly elevated pSTAT3 levels whereas IFN-γ stimulation resulted in significantly reduced pSTAT5 levels. CD4+ T cell subsets showed reduced pSTAT3 induction in response to multiple cytokine stimuli, and reduced pSTAT1 and pSTAT5 induction with IFN-γ. Similar reductions in pSTAT3 and pSTAT5 induction were seen in CD8+CD45RA+ T cells with several cytokine stimuli. In monocytes, IL-7 and IL-21 stimulation resulted in significantly decreased pSTAT1 levels. No significant changes in pSTAT signaling was found in non-B non-T cells after stimulation with various cytokines. In addition, acute opioid withdrawal via intravenous naloxone resulted in significantly increased pSTAT1 and pSTAT5 levels after IFN-γ stimulation in CD8+ T cells. Conclusion One month of opioid exposure significantly reduced cytokine-induced levels of phospho-STAT signaling. These findings suggest that chronic opioid exposure suppresses immune signaling pathways.