Calcitonin gene-related peptide effects on phenotype and IL-12 production of monocyte-derived dendritic cells in rheumatoid arthritis patients

ABSTRACT

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 [CDRP], as a multifunctional neuropeptide. DCs were generated from isolated monocytes from four resistant and two early female RA patients using IL-4, 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. 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. 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