ABSTRACT
Psoriasis is an autoimmune and inflammatory skin disease. Psoriatic patients express higher levels of plasma homocysteine (Hcy) concentration and pro-inflammatory mediators than healthy people; this is frequently associated with vitamin D deficiency. The aim of this clinical study was to investigate the effects of high doses of vitamin D supplementation on the parameters of Hcy metabolism and cytokines in sera of psoriatic patients. This prospective study was conducted on 40 psoriatic patients who had the vitamin D deficiency. All patients received vitamin D 5000 IU/day for three months. Clinical and biochemical measurements were taken at baseline and at follow up (3 months). The results showed that the severity of clinical features, measured by the psoriasis area severity index (PASI) score, were considerably improved in patients after vitamin D supplementation. After vitamin D supplementation, most of the patients (n = 25 or 62.5%) had mild clinical form (p < 0.001). After twelve weeks of intervention period, there were significant increases in vitamin D and B12 serum levels in comparison to the levels that had been measured at the beginning of the study (56.77 ± 14.66 nmol/L and 301.08 ± 95.02 pg/mL vs. 103.85 ± 32.20 nmol/L and 362.81 ± 118.56 pg/mL, respectively; p < 0.001). Moreover, serum levels of Hcy and folate were significantly lower at the end of the study in comparison with the initial levels (12.45 ± 1.92 µmol/L and 8.01 ± 3.88 mg/mL vs. 10.38 ± 1.66 µmol/L and 6.27 ± 2.60 mg/mL, respectively). High doses of vitamin D supplementation led to a significant decrease in pro-inflammatory cytokines (IFN-ɤ, TNF-α, IL-1ß, IL-6, IL-8, and IL-17) and high-sensitivity C-reactive protein (hsCRP), whereas the production of anti-inflammatory cytokines (IL-10, IL-5) was up-regulated. In conclusion, supplementation with high doses of vitamin D could be one of the possible preventive and therapeutic measures to reduce systemic inflammation in psoriatic patients.
Subject(s)
Cytokines/blood , Homocysteine/blood , Psoriasis/drug therapy , Vitamin D Deficiency/drug therapy , Vitamin D/administration & dosage , Adult , Aged , Biomarkers/blood , Cytokines/drug effects , Dietary Supplements , Female , Gene Expression Regulation/drug effects , Homocysteine/drug effects , Humans , Male , Middle Aged , Patient Acuity , Prospective Studies , Psoriasis/blood , Vitamin B 12/blood , Vitamin D/pharmacology , Vitamin D Deficiency/bloodABSTRACT
Mesenchymal stem/stromal cells (MSCs, having both multi-potent differentiation potential and prominent immunomodulatory properties, are seen as a very powerful tool for the therapy of diseases characterized by tissue damage and/or unregulated immune responses. Dendritic cells (DCs are key immunoregulatory cells at the crossroads between immunity and tolerance, able to fine-tune the whole immune response via regulation of adaptive immunity. Therefore, untangling the complex interactions between DCs and MSCs is crucial for understanding various mechanisms involved in the pathogenesis of immune-related diseases and for the discovery of new therapeutic targets for advanced treatment procedures. From this perspective, we reviewed the data that have been obtained to date regarding the complex effects of MSCs on DC development and functions, delineating the abundant mechanisms involved in these interactions. Additionally, we have pointed out to additional mechanisms of MSC/DC cross-talk that have not been directly proven, but that could have a significant role, not only in DC functions and the maintenance of immune homeostasis, but also in migration, differentiation and the functions of MSCs. For now, much more is known about the influence of MSCs on DCs than vice versa, so more studies should be done in order to fully understand this cross-talk.