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
ABSTRACT
Systemic Lupus Eyrythematosus [SLE] is an autoimmune disease characterized by antibodies to nuclear antigens, particularly anti-dsDNA. Imbalance between production and destruction of immune cells causes cytopenia. Sex hormones have im-munomodulatory effects; estrogen increases the production of autoantibodies in SLE prone NZB/NZW mice. To investigate the relationship between sex hormones, anti-dsDNA, and lymphocyte subsets in Iranian patients with SLE. 38 SLE patients [28 females and 10 males] meeting 4 of 11 ACR revised criteria for SLE classification, and 20 age and sex matched healthy individuals [10 females and 10 males] participated in this study. Lymphocyte subsets were analyzed using flow cy-tometric analysis. Serum anti-dsDNA levels and sex hormones concentrations were determined using commercial ELISA and RIA kits, respectively. The absolute count of white blood cells, lymphocytes, T lymphocytes [CD3[+], T helper cells [CD3[+]CD4[+], B cells [CD19[+] and Nk cells [CD3[-] CD16[+]CD56[+] in SLE patients diminished significantly in comparison to control group [p<0.05]. IgG anti-dsDNA antibody levels were significantly higher in patients compared to controls as expected [p<0.05]. Prolactin increased significantly, while DHEAS showed a significant decrease in SLE patients compared with the controls [p<0.05], however the level of estrogen did not have any significant difference in SLE patients in comparison to controls. Increased concentration of prolactin together with a simultaneous decrease in serum DHEAS in SLE patients are associated with anti-dsDNA elevation and a decrease in almost all lymphocyte subsets