Low levels of serum vitamin D in clozapine-treated schizophrenia patients are associated with high levels of the proinflammatory cytokine IL-6

Krivoy, Amir; Satz, Joshua; Hornfeld, Shay Henry; Bar, Lior; Gaughran, Fiona; Shoval, Gal; Hochman, Eldar; Weizman, Abraham; Taler, Michal

doi:10.1097/yic.0000000000000303

Cited by 8 publications

(11 citation statements)

References 47 publications

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“…Clinical studies have shown that there is a close relationship between vitamin D and IL-6 in many diseases. Lower levels of serum vitamin D were associated with higher levels of IL-6 in HIV-infected or clozapine-treated schizophrenia patients [39,40]. Conversely, supplementation with vitamin D can reduce IL-6 levels in multiple sclerosis [41].…”

Section: Discussionmentioning

confidence: 95%

Vitamin D Improves the Effect of Glucocorticoids on Attenuating Lipopolysaccharide-Induced IL-6 Production via TLR4/NF-κB Pathway in Human Respiratory Epithelial Cells

Wang

Zhao

Yao

et al. 2022

Int Arch Allergy Immunol

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Background: Glucocorticoid (GC) resistance results in unsatisfactory outcomes in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Previous studies have shown that calcitriol, the active form of vitamin D, alone or in combination with corticosteroids, exerts crucial immunomodulatory effects on inflammatory responses. However, whether vitamin D can improve the effect of GCs to attenuate inflammation in the epithelium of CRSwNP remains unclear. Methods: A human bronchial epithelial cell line (Beas-2B) and primary human nasal epithelial cells (HNECs) obtained from 10 patients with CRSwNP were exposed to lipopolysaccharide (LPS) for 24 h to establish an inflammation model. LPS-stimulated HNECs and Beas-2B cells were treated with/without dexamethasone in the presence or absence of calcitriol pretreatment for 24 h. The expression levels of interleukin-6 (IL-6) mRNA and protein were determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Toll-like receptor 4 (TLR4)/NF-κB pathway related markers were examined by western blotting. One-way ANOVA or the Kruskal-Wallis test with post hoc analysis were used for multiple comparisons among groups. Results: The production of IL-6 in Beas-2B cells and primary HNECs after LPS stimulation was significantly increased, which could be inhibited by dexamethasone or calcitriol alone. However, significant inhibition of IL-6 production was observed in the calcitriol plus dexamethasone group. Further analysis showed that calcitriol could enhance the effect of dexamethasone in inhibiting LPS-induced overexpression of TLR4, Myd88, and phosphorylation of p65. Conclusion: Our findings demonstrated that vitamin D could improve the effect of GCs to alleviate the level of IL-6 induced by LPS via the TLR4/NF-κB pathway in human respiratory epithelial cells.

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Section: Discussionmentioning

confidence: 95%

Vitamin D Improves the Effect of Glucocorticoids on Attenuating Lipopolysaccharide-Induced IL-6 Production via TLR4/NF-κB Pathway in Human Respiratory Epithelial Cells

Wang

Zhao

Yao

et al. 2022

Int Arch Allergy Immunol

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“…Not only the innate immune system, but also adaptive immunity has been suggested to be affected by vitamin D. For instance, vitamin D modulates the differentiation and activation of CD 4 + lymphocytes via binding to VDRs on T cells [21]. However, at the same time, it inhibits the production of proinflammatory cytokines, including IL-2, IL-17, and IFN-ɤ [22]. Vitamin D has also been mentioned as suppressing the proliferation and immunoglobulin production of B cells and their differentiation to plasma cells [23].…”

Section: Discussionmentioning

confidence: 99%

Is There Any Relationship between Maternal Vitamin D Levels and Asymptomatic Bacteriuria? A Preliminary Study

Ozdes¹,

Avcı²,

Çelik³

et al. 2020

OJOG

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“…19 14 research articles reported the cross-sectional comparisons of the levels of multiple inflammatory markers other than CRP between the clozapine treatment group and healthy control group. 15,16,[20][21][22][23][24][25][26][27][28][29][30][31] Six studies 16,[20][21][22][23][24] performed group comparisons of the peripheral level of interleukin-6 (IL-6), a proinflammatory cytokine, three [22][23][24] of which identified significance differences with higher IL-6 observed in the patient group receiving chronic clozapine treatment than healthy controls. Higher peripheral IL-6 was also associated with lower vitamin D level in patients on clozapine treatment.…”

Section: The Impact Of Clozapine On Inflammatory Markersmentioning

confidence: 99%

A systematic review of clozapine‐associated inflammation and related monitoring

Leung,

Zhang,

Markota

et al. 2023

Pharmacotherapy

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Clozapine is an effective antipsychotic medication used for treatment‐resistant schizophrenia. However, it is underutilized due to rigorous hematologic monitoring requirements and many adverse drug reactions. Publications have highlighted the occurrence of inflammatory reactions, some life‐threatening, particularly during the early stages of clozapine treatment. Although guidelines have suggested monitoring for inflammatory processes during clozapine initiation, screening in clinical practice is not universal. This systematic review aimed to investigate the relationship between clozapine and inflammation and assess the importance of monitoring for inflammatory reactions. A comprehensive literature search yielded 6,915 unique publication records after removal of duplicates. After a rigorous screening process, 75 publications were included in the review, which focused on three main aspects: i) the impact of clozapine on inflammatory markers, ii) monitoring cardiac and other organ function during clozapine‐associated inflammatory processes, and iii) monitoring non‐specific signs and symptoms of inflammation. Elevated levels of C‐reactive protein (CRP) and several proinflammatory cytokines have been observed in association with clozapine treatment. However, the practicality of measuring specific markers in clinical practice remains uncertain. Current evidence supports monitoring CRP levels during the first 4 to 8 weeks of treatment, especially to facilitate myocarditis screening. Further research is needed to establish clinically‐relevant CRP thresholds for intervention. The implementation of monitoring protocols during the early phase of clozapine treatment may mitigate adverse reactions and allow for continued use of clozapine. Future studies should also explore the association between clozapine‐associated inflammation and pneumonia, as well as investigate the impact of inflammation on clozapine metabolism to predict the need for dose adjustment. These endeavors may facilitate the development and implementation of evidence‐based guidelines for the monitoring of clozapine‐associated inflammation.

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Low levels of serum vitamin D in clozapine-treated schizophrenia patients are associated with high levels of the proinflammatory cytokine IL-6

Cited by 8 publications

References 47 publications

Vitamin D Improves the Effect of Glucocorticoids on Attenuating Lipopolysaccharide-Induced IL-6 Production via TLR4/NF-κB Pathway in Human Respiratory Epithelial Cells

Vitamin D Improves the Effect of Glucocorticoids on Attenuating Lipopolysaccharide-Induced IL-6 Production via TLR4/NF-κB Pathway in Human Respiratory Epithelial Cells

Is There Any Relationship between Maternal Vitamin D Levels and Asymptomatic Bacteriuria? A Preliminary Study

A systematic review of clozapine‐associated inflammation and related monitoring

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