Positive correlation between levels of IL-1 or IL-2 and 1,25(OH)2D/25-OH-D ratio in synovial fluid of patients with rheumatoid arthritis

Inaba, Masaaki; Yukioka, Kazuhiko; Furumitsu, Yutaka; Murano, Mayuko; Goto, Hitoshi; Nishizawà, Yoshiki; Morii, Hirotoshi

doi:10.1016/s0024-3205(97)00602-4

Cited by 28 publications

(20 citation statements)

References 29 publications

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“…Instead, the 1,25(OH)2D3 molecules produced in these tissues act through intracrine and paracrine mechanisms to regulate VDRdependent activities of the local cells. However, excessive production of 1,25(OH)2D3 in extrarenal tissues can result in spilling over of 1,25(OH)2D3 to the blood circulation, thus raising blood levels of 1,25(OH)2D3, which in turn can cause hypercalcemia [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]. Therefore, extrarenal production of 1,25(OH)2D3 can have deleterious consequences, such as the development of acute pancreatitis as discussed below.…”

Section: Vitamin D Metabolism In Extrarenal Tissuesmentioning

confidence: 99%

“…It is important to note that there is accelerated CYP27B1-catalyzed conversion of 25(OH)D3 to 1,25(OH)2D3 by activated macrophages in the extrarenal tissues undergoing inflammation [16]. This explains why patients with different inflammatory diseases, such as sarcoidosis [17][18][19][20][21], rheumatoid arthritis [22][23][24][25], pulmonary tuberculosis [26][27][28][29], inflammatory bowel disease [30][31][32] and leprosy [33], have elevated blood levels of 1,25(OH)2D3 and develop hypercalcemia.It should be noted that the synthesis of 1,25(OH)2D3 in extrarenal tissues is not intended to raise the systemic level of 1,25(OH)2D3. Instead, the 1,25(OH)2D3 molecules produced in these tissues act through intracrine and paracrine mechanisms to regulate VDRdependent activities of the local cells.…”

mentioning

confidence: 99%

“…In addition, individuals who use excessive amounts of vitamin D or biologically active synthetic analogs of vitamin D may not only develop hypercalcemia, but also acute pancreatitis ( Table 1). Given that inflammation in various tissues is a major cause of extrarenal synthesis of 1,25(OH)2D3 [16,[18][19][20][21][22][23][24][25][26][27][28][29][30][31][32], it is not surprising that epidemiological studies have found high incidence of acute pancreatitis in patients with rheumatoid arthritis or systemic lupus erythematous disease [49][50][51][52].Sarcoidosis is another inflammatory disorder that is characterized by the presence of granulomas, mainly in lymph nodes and pulmonary tissues, that serve to "quarantine" infectious microorganisms and/or other foreign particles when the immune system fails to eliminate them [53]. The granulomas contain large numbers of activated macrophages that use CYP27B1 to actively convert 25(OH)D3 to 1,25(OH)2D3 [18][19][20][21].…”

mentioning

confidence: 99%

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Vitamin D Deficiency in Patients with Pancreatitis: Is Vitamin D Replacement Required?

Han¹,

Margulies²

2016

Pancreat Disord Ther

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Clinical findings have shown that approximately 40% of patients with pancreatitis, acute or chronic, have severe vitamin D deficiency; this can reach up to 60% of patients with chronic pancreatitis. These findings raise an important question: Is vitamin D deficiency a cause or a result of pancreatitis? The answer(s) to this question is clinically important given that high oral doses of vitamin D supplementation are widely prescribed for individuals with vitamin D deficiency. Considering that there is active conversion of 25(OH)D3 to 1,25(OH)2D3 by activated macrophages in tissues undergoing inflammation, that elevation of the blood levels of 1,25(OH)2D3 levels can cause hypercalcemia, that hypercalcemia can precipitate pancreatitis, that excessive use of vitamin D supplementation can cause acute pancreatitis and that sarcoidosis causes elevated blood levels of 1,25(OH)2D3, hypercalcemia and acute pancreatitis, it is reasonable to consider both 25(OH)D3 and 1,25(OH)2D3 as negative acute-phase reactants, specifically in the context of the pathogenesis of pancreatitis. Thus, down-regulation of blood levels of 25(OH)D3 and 1,25(OH)2D3 in patients with pancreatitis appears to be a protective mechanism to prevent the development hypercalcemia, which would exacerbate the pancreatitis. Therefore, it is reasonable to consider that vitamin D replacement treatment may produce more harm than benefit for patients with pancreatitis.Keywords: Vitamin D deficiency; Inflammation; Acute pancreatitis; Sarcoidosis; Negative-Phasereactant; Hypercalcemia Classic View of Vitamin D MetabolismUnlike most other vitamins that are dietary essential nutrients for the human body, vitamin D is synthesized in the human body and acts like a steroid hormone [1]. As outlined in Figure 1, vitamin D metabolism in the human body starts with the UVB (ultraviolet light B) photon-stimulated structural change in 7-dehydrocholesterol to yield vitamin D3 in the epidermis of the skin. Vitamin D3 is then converted to the biologically active 1,25(OH)2D3 through two sequential hydroxylation reactions. Vitamin D3 is first hydroxylated mainly by the enzyme, CYP2R1, to become 25(OH)D3 in the liver; then 25(OH)D3 is hydroxylated to become 1,25(OH)2D3 by the enzyme, CYP27B1, in the epithelial cells of the proximal convoluted tubule in the kidney [1]. PTH (parathyroid hormone), which is released by the parathyroid glands in response to decreasing blood calcium level, stimulates CYP27B1 activity in the epithelial cells of the proximal convoluted tubules in the kidney, thereby regulating the rate of renal conversion of 25(OH)D3 to 1,25(OH)2D3 [1]. The PTHregulated renal production of 1,25(OH)2D3 is the primary source of the 1,25(OH)2D3 in the blood circulation because individuals with renal failure have decreased blood levels of 1,25(OH)2D3 [2]. The biologically active 1,25(OH)2D3 binds to and stimulates the transcription activity of the nuclear VDR (vitamin D receptor) in target cells to regulate expression of genes, thus changing cellular activities [1]. Sp...

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Section: Vitamin D Metabolism In Extrarenal Tissuesmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Vitamin D Deficiency in Patients with Pancreatitis: Is Vitamin D Replacement Required?

Han¹,

Margulies²

2016

Pancreat Disord Ther

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“…33 The paradoxic decrease in serum levels of 1,25-(OH) 2 D 3 despite an increase in 1␣-hydroxylase protein may also be due to decreases in 1␣-hydroxylase activity. Indeed, the ratio [1,25-(OH) 2 D 3 /25-(OH)D 3 ], commonly used as an index of the 1␣-hydroxylase activity, 34 is reduced in 5/6Nx-F rats. 1␣-Hydroxylase is also a mitochondrial cytochrome P450, which, like the other hepatic CYP proteins mentioned, is NADPH dependent.…”

Section: The 125-hydroxylationmentioning

confidence: 99%

Dietary Fructose Inhibits Intestinal Calcium Absorption and Induces Vitamin D Insufficiency in CKD

Douard

Asgerally²,

Sabbagh³

et al. 2010

Journal of the American Society of Nephrology

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Renal disease leads to perturbations in calcium and phosphate homeostasis and vitamin D metabolism. Dietary fructose aggravates chronic kidney disease (CKD), but whether it also worsens CKD-induced derangements in calcium and phosphate homeostasis is unknown. Here, we fed rats diets containing 60% glucose or fructose for 1 mo beginning 6 wk after 5/6 nephrectomy or sham operation. Nephrectomized rats had markedly greater kidney weight, blood urea nitrogen, and serum levels of creatinine, phosphate, and calcium-phosphate product; dietary fructose significantly exacerbated all of these outcomes. Expression and activity of intestinal phosphate transporter, which did not change after nephrectomy or dietary fructose, did not correlate with hyperphosphatemia in 5/6-nephrectomized rats. Intestinal transport of calcium, however, decreased with dietary fructose, probably because of fructosemediated downregulation of calbindin 9k. Serum calcium levels, however, were unaffected by nephrectomy and diet. Finally, only 5/6-nephrectomized rats that received dietary fructose demonstrated marked reductions in 25-hydroxyvitamin D 3 and 1,25-dihydroxyvitamin D 3 levels, despite upregulation of 1␣-hydroxylase. In summary, excess dietary fructose inhibits intestinal calcium absorption, induces marked vitamin D insufficiency in CKD, and exacerbates other classical symptoms of the disease. Future studies should evaluate the relevance of monitoring fructose consumption in patients with CKD.

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“…8,9 Within the rheumatoid joint, the active form of vitamin D has been shown to be synthesized in RA synovium and is thought to be stimulated by interleukin-1 (IL-1) and/or IL-2. 10 The actions of 1,25 (OH) 2 D 3 are mediated via the nuclear VDR. Its gene, located on chromosome 12q12-14, harbors several polymorphisms and was found to be associated with several autoimmune diseases such as Addison's disease, type I diabetes and systemic lupus erythematosus.…”

Section: Introductionmentioning

confidence: 99%

Association study of VDR gene with rheumatoid arthritis in the French population

et al. 2005

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Positive correlation between levels of IL-1 or IL-2 and 1,25(OH)2D/25-OH-D ratio in synovial fluid of patients with rheumatoid arthritis

Cited by 28 publications

References 29 publications

Vitamin D Deficiency in Patients with Pancreatitis: Is Vitamin D Replacement Required?

Vitamin D Deficiency in Patients with Pancreatitis: Is Vitamin D Replacement Required?

Dietary Fructose Inhibits Intestinal Calcium Absorption and Induces Vitamin D Insufficiency in CKD

Association study of VDR gene with rheumatoid arthritis in the French population

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