An investigation into the modulation of T cell phenotypes by amitriptyline and nortriptyline

Amitriptyline is prescribed for treating the symptoms of neuroinflammatory disorders including neuropathic pain and fibromyalgia. As amitriptyline has evidence of modulating the neuroimmune interface; the effects of amitriptyline treatment on T-cell phenotype and function were examined in vitro. Peripheral blood mononuclear cells(PBMCs) were isolated and treated with amitriptyline, nortriptyline and a combination of both drugs. Toxicity for T-cells was assessed by Annexin V/Propidium Iodide staining. Activation status and cytokine expression by T-cells post treatment was assessed by flow cytometry. The levels of secreted cytokines, chemokines and neurotrophins were measured by ELISA in the supernatants. There was no significant increase in T-cell death following 24 or 48 h compared to controls. There were significantly lower frequencies of CD8⁺ T-cells after treatment with amitriptyline, nortriptyline and a combination of both compared to a Vehicle Control(VC)(p<0.001). The frequencies of naive CD8⁺CD45RA⁺ cells were significantly lower after amitriptyline, nortriptyline and a combination of both (p<0001). The frequencies of CD27⁺CD4⁺(p<0.05) and CD27⁺CD8⁺(p<0.01) T-cells were also significantly lower following combination drug treatment. Significantly lower frequencies of IFN-γ-producing CD8⁺ T-cells were observed with all treatment combinations(p<0.05) and frequencies of IL-17-producing CD4⁺ and CD8⁺ T-cells were significantly lower following amitriptyline treatment (p<0.05). Frequencies of Natural Killer T-cells were significantly higher following treatment with nortriptyline (p<0.05). Significantly higher levels of IL-16 (p<0.001) and lower levels of TNF-β (p<0.05) were observed in supernatants. This data indicates that both amitriptyline and nortriptyline modulate the phenotype and function of T-cells and this may have clinical relevance in the pathologies of its off-label applications.