Calcitonin Gene-Related Peptide Effects on Phenotype and IL-12 Production of Monocyte-Derived Dendritic Cells in Rheumatoid Arthritis Patients

Abstract

Objective(s) Recent studies on human indicate that the introduction of therapeutic use of tolerogenic dendritic cell (DC) for chronic inflammatory conditions is imminent. For the purpose of defining CGRP potency in tolerogenic DC production, we investigated the phenotype and IL-12 production of DCs generated from the monocytes of rheumatoid arthritis (RA) patients in the presence of the calcitonin gene-related peptide (CGRP), as a multifunctional neuropeptide. Materials and Methods DCs were generated from isolated monocytes from four resistant and two early female RA patients using IL4, GM-CSF, and CGRP at concentrations of 0, 1, and 100 nM. Then, the phenotype of neuropeptide-treated or untreated DCs was determined using flow cytometry and the IL-12 production was measured by ELISA. Results Our study showed that, on the last day of the culture, at a concentration of 1 nM CGRP, the mean fluorescence intensity (MFI) for CD80 increased (14.13%) and the MFIs for CD83, CD86, and HLA-DR decreased (14.57%, 5.28%, and 6.88% respectively). Moreover, at 100 nM CGRP concentration, the MFI for CD80 increased (11.10%) and the MFIs for CD83, CD86, and HLA-DR decreased (4.27%, 18.60%, and 19.75% respectively). In addition, our results indicated that the mean concentrations of IL-12 produced at 0, 1, and 100 nm CGRP concentrations measured 13.72±2.41, 11.01±1.61, and 7±1.34 pg/ml respectively. Conclusion Decreased CD83, CD86, and HLA-DR expression and reduced IL-12 production by CGRP were found in the RA patients' monocyte-derived DCs. CD83 is a well-defined DC activation marker. HLA-DR and CD86 are appropriate molecules for inducing an immune response. IL-12 promotes cell-mediated immunity. Therefore we suggest that CGRP may be used as an inducer in the production of tolerogenic DCs.