Vitamin D and Cytokine Profiles in Patients With Systemic Sclerosis

Abstract

Introduction Hypovitaminosis D has been frequently described in systemic sclerosis (SSc). Cytokines are important mediators of tissue damage and clinical dysfunction in SSc and may be influenced by vitamin D levels. Objective To evaluate the serum levels of vitamin D and its correlation with the clinical features and cytokine profiles in SSc patients. Methods Case-control study, including 50 SSc patients and 35 healthy non matched controls. Serum levels of 25(OH) vitamin D were measured by chemiluminescence assay, and serum concentrations of interleukin 2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor, and interferon γ were determined by flow cytometry. Results Fourteen patients (28%) had diffuse cutaneous SSc, 94% were female, 80% European derived, with a mean age of 57.2 ± 12.8 years. The serum vitamin D levels in SSc patients were 23.9 ± 8.5 ng/mL and 30.2 ± 6.2 ng/mL in the control group (standardized mean difference −6.19; 95% confidence interval, −9.9 to −2.3; p = 0.002), despite the more frequent supplementation of vitamin D in SSc patients (p = 0.014). No significant associations were found among vitamin D concentrations and cytokine levels. Serum levels of IL-6 were significantly elevated in SSc patients (p = 0.024) and were positively correlated with the modified Rodnan skin score (r s = 0.291, p =0.041). Conclusions Despite lower vitamin D levels in SSc patients, there was no clear association with any cytokine. Serum levels of IL-6 were significantly elevated and positively correlated with the extent of skin involvement in SSc patients.

Role of Vitamin D in Systemic Sclerosis: A Systematic Literature Review

“…The prevalence of hypovitaminosis D in SSc remains a topic of interest, and several papers have aimed to investigate the association between serum vitamin D levels and different aspects of SSc. Overall, irrespective of the clinical and serological disease settings, SSc patients present with lower levels of vitamin D compared with healthy controls [ 12 , 14 , 15 , 19 , 20 , 23 – 26 , 31 , 35 , 37 , 44 , 45 ]. Although hypovitaminosis D is frequently reported, some authors have found significantly lower levels ( p < 0.001) and vitamin D deficiency [ 15 , 19 , 20 , 25 , 31 , 35 , 37 ], while others have found only insufficient levels.…”

“…Some studies have focused on statistically significant relationships between vitamin D and parathyroid hormone (PTH), not only in healthy individuals but also in SSc patients [ 12 , 13 , 31 , 35 , 46 ]. Furthermore, Hax et al demonstrated that 25-hydroxyvitamin D [25(OH)D] levels are inversely correlated with PTH [ 12 ]. Paolino et al identified significant differences in malnourished SSc patients in the median values of PTH and vitamin D levels [ 13 ].…”

“…Liberto et al observed a significantly increased production of Treg cells and IL-10 following 1,25(OH) vitamin D treatment, suggesting a beneficial role of vitamin D supplementation in autoimmunity [ 17 ]. In a case-control study, Hax et al demonstrated that IL-2 and IL-4 serum levels were reduced in SSc patients compared with controls; however, no significant correlation between cytokines and serum levels of vitamin D was demonstrated in such patients [ 12 ].…”

25-hydroxyvitamin D3 Levels and Their Clinical Associations in a Polish Cohort of Systemic Sclerosis Patients: A Cross-Sectional Study

“…Consequently, we cannot draw definite conclusions with such small sample sizes and a relatively weak link, which was not confirmed with the Spearman's correlation. Moreover, Hax et al demonstrated increased levels of interleukin 6 that positively (albeit weakly) correlated with the modified Rodnan skin score (r = 0.291, p = 0.041) in their SSc group [32]. Interestingly, Caramaschi et al, as well as Vacca et al [30], reported a link between increased ESR and vitamin D deficiency, which we could not corroborate.…”

Investigation of the Expression of Inflammatory Markers in Oral Biofilm Samples in Patients with Systemic Scleroderma and the Association with Clinical Periodontal Parameters—A Preliminary Study

“…Moreover, different Th1 cell-associated cytokines or immunomodulatory mediators have been found in patients with SSc. Increased expression of the proinflammatory IL-2 and IL-6 has been detected in cell cultures derived from peripheral mononuclear cells and serum of patients with SSc [10][11][12][13]. The concentration of anti-inflammatory IL-10 was increased among patients with SSc in in vitro cultures with non-stimulated peripheral blood mononuclear cells [14].…”