A Study on Vitamin D and Cathelicidin Status in Patients with Rosacea: Serum Level and Tissue Expression

BACKGROUND: Rosacea is a chronic inflammatory disease characterized by centrofacial erythema. Excess cathelicidin is suggested to be important to the pathophysiology of the disease. Recently, presence of a vitamin D response element was revealed in the cathelicidin gene promoter. OBJECTIVE: The aim of this study was to determine whether vitamin D and cathelicidin are associated with rosacea, both serologically and histopathologically. METHODS: Subjects with rosacea and without chronic skin disorders were enrolled in the patient and control groups, respectively. Serum 25-hydroxy-vitamin D and cathelicidin levels were measured. Tissue expression of cathelicidin and vitamin D receptor were measured with immunostaining-intensity-distribution index. RESULTS: The mean serum 25-hydroxyvitamin D level of patients with rosacea was 12.18±5.65 ng/ml, which is lower than that of the controls (17.41±6.75 ng/ml). Mean serum cathelicidin levels in patients with rosacea and the controls were 85.0±26.1 ng/ml and 55.0±23.3 ng/ml, respectively. Cathelicidin expression in rosacea tissue was significantly higher than that in control tissue (5.21 vs. 4.03). No significant difference was observed in vitamin D receptor expression. CONCLUSION: Higher cathelicidin expression in rosacea supports the hypothesis that an abnormal inflammatory response of the innate immune system is important in pathogenesis of rosacea, but the role of high cathelicidin serum levels is complicated. Serum vitamin D was lower in patients with rosacea, although serum cathelicidin was higher than that of the controls. This suggests that the role of vitamin D level in the pathogenesis of rosacea merits further investigation.

Efeito da suplementação com vitamina D sobre adipocinas em idosos obesos com osteoporose / Effects of vitamin D supplementation on adipokines in obese osteoporotic subjects

Uma das principais consequências do envelhecimento populacional é o aumento dos índices de osteoporose, que resulta em risco aumentado de fratura, sobretudo as fraturas relacionadas com traumas de pequena intensidade. Similarmente, a obesidade está sendo diagnosticada em um percentual cada vez maior de indivíduos e, atualmente, acredita-se que mais de meio bilhão da população mundial seja obesa. A vitamina D, dentre as suas funções, desempenha um papel central na homeostase do cálcio e do fósforo e tem sua ação reduzida em indivíduos obesos, possivelmente em consequência do seu sequestro no tecido adiposo. O tecido adiposo é um órgão endócrino capaz de produzir e secretar peptídeos bioativos como leptina, fator de necrose tumoral α (TNF-α) e adiponectina que atuam simultaneamente em algumas vias de regulação do metabolismo energético e ósseo. O objetivo do presente estudo foi avaliar a resposta ao tratamento com suplementação de cálcio e vitamina D sobre marcadores sanguíneos do metabolismo ósseo e energético e do estado inflamatório crônico em 21 pacientes obesos e osteoporóticos com hipovitaminose D, em tratamento com bisfosfonatos durante 12 meses. A idade dos pacientes variou entre 63-86 anos e 20/21 eram mulheres em uso de ácido zoledrônico (47,6%) ou alendronato de sódio (52,4%). Durante o período de acompanhamento não houve alteração do estado nutricional dos pacientes, que permaneceram obesos. Após os 12 meses de tratamento os níveis séricos de vitamina D, osteoprotegerina e adiponectina aumentaram significativamente em relação à medida basal. No mesmo período e nas mesmas condições, os níveis séricos de C-telopeptídeo, fosfatase alcalina óssea, leptina e TNF-α apresentaram redução significativa em relação aos níveis basais pré-tratamento. Apesar da suplementação oral, os níveis de vitamina D mesmo tendo aumentado significativamente em relação aos valores pré-tratamento, permaneceram abaixo da faixa de referência de normalidade. O efeito anti-reabsortivo dos bisfosfonatos foi confirmado e, aparentemente, foi independente do estado de obesidade. A maior disponibilidade de reservatórios de gordura e a alta liposolubilidade da vitamina D, favorecendo o seu sequestro neste sítio, provavelmente resultou na redução da sua biodisponibilidade que poderia explicar a manutenção do estado de hipovitaminose D, a despeito da suplementação durante 12 meses com cálcio e vitamina D. Nossos resultados estão de acordo com os relatos da literatura que favorecem a hipótese de que leptina e adiponectina são sensíveis à ação da vitamina D, caracterizada por uma relação direta entre vitamina D e adiponectina e inversa entre vitamina D e leptina. A ação anti-inflamatória da 25(OH)D, avaliada através da redução dos níveis circulantes de TNF-α também pode ser sugerida a partir dos resultados do presente estudo. Estudos clínicos adicionais serão necessários para tentar elucidar os mecanismos sistêmicos, as interações e níveis circulantes ótimos de vitamina D e adipocinas em obesos e o seu papel na saúde humana

One of the main consequences of population aging is the rising in osteoporosis rates, resulting in increased risk of fracture, particularly fragility fractures. Similarly, obesity is being diagnosed in an increasing percentage of individuals, and currently it is believed that more than half a billion of the world population is obese. Vitamin D, among its many functions, plays a central role in the homeostasis of calcium and phosphorus and has an effect reduced in obese individuals possibly in consequence of sequestration in adipose tissue. The adipose tissue is an endocrine organ able to produce and secrete bioactive peptides such as leptin, tumor necrosis factor α (TNF-α) and adiponectin that simultaneously act in some pathways regulating energy and bone metabolism. The aim of this study was to evaluate the response to treatment with calcium and vitamin D supplementation on blood markers of bone and energy metabolism and a marker of chronic inflammatory state in 21 obese and osteoporotic patients with hypovitaminosis D, treated with bisphosphonates for 12 months. The patients' ages ranged from 63-86 years and 20/21 was women taking zoledronic acid (47.6%) or sodium alendronate (52.4%). During the follow-up period there was no change in the nutritional status of patients who remained obese. After 12 months of treatment serum levels of vitamin D, osteoprotegerin and adiponectin increased significantly compared to baseline values. In the same period and under the same conditions, C-telopeptide, serum bone alkaline phosphatase, leptin and TNF-α showed significant reduction compared to baseline levels. Compared to pre-treatment values, oral supplementation with vitamin D increased significantly the circulating levels that, however, remained below the normal reference range. The anti-resorptive effect of bisphosphonates was confirmed and was apparently independent of the state of obesity. The greater availability of fat reservoirs and the high lipid solubility of vitamin D, favoring its sequestration on this site, probably resulted in reduced bioavailability and thus, persistence of the state of hypovitaminosis D, despite the 12 months supplementation with calcium and vitamin D. Our results are in agreement with most reports from the literature that favor the hypothesis that leptin and adiponectin are sensitive to the action of vitamin D, characterized by a direct relationship between adiponectin and vitamin D and a negative relationship between vitamin D and leptin. The anti-inflammatory action of 25 (OH) D, as measured by the reduction in circulating levels of TNF-α, can also be suggested from the results of this study. Additional clinical studies are needed to try to elucidate the systemic mechanisms, interactions and optimal circulating levels of vitamin D and adipokines in obese and their role in human health

Vitamin D, the Cutaneous Barrier, Antimicrobial Peptides and Allergies: Is There a Link?

Atopic diseases such as atopic dermatitis (AD) are very common in industrialized countries. Up to 15%-30% of all children and 2%-10% of all adults suffer from AD. Already in early disease stages, a defective epidermal barrier is known to contribute to the pathogenesis of AD. Central elements in the epidermal barrier are antimicrobial peptides (AMPs), which are secreted by keratinocytes, sweat gland cells but also infiltrating immune cells. AMPs function as endogenous antibiotics and are able to kill bacteria, viruses, and fungi. Furthermore AMPs act as immune modulators with effects on the innate and adaptive immune system. The probably best studied AMPs in human skin are the defensins and cathelicidin. In atopic diseases the functions of AMPs such as cathelicidin might be impaired and microbial superinfections could serve as cofactors for allergic sensitization. Hence, induction of AMPs could be beneficial in these patients. Cathelicidin which is often referred to its peptide form hCAP18 or LL-37 can be induced by ultraviolet light B (UVB) irradiation and is upregulated in infected and injured skin. The cathelicidin gene carries a vitamin D response element and the vitamin D pathway could therefore be targeted for cathelicidin regulation. As the development and course of atopic diseases might be influenced by vitamin D signaling these pathomechanisms could explain the growing evidence connecting vitamin D to allergic diseases, including AD, allergic rhinitis, food allergies and asthma. In this review the role of vitamin D and the AMP cathelicidin in the pathogenesis of atopic diseases with impaired barrier function will be discussed.