Review of lithium effects on immune cells

Maddu, Narendra; Raghavendra, Pongali B.

doi:10.3109/08923973.2014.998369

Cited by 37 publications

(33 citation statements)

References 74 publications

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“…It is well-known that increasing the cortex in relation to the medulla ratio increased the number of T-lymphoblasts and increased the T-lymphocyte, which reflects on stimulating cellular immunity (84)(85)(86).…”

Section: Discussionmentioning

confidence: 99%

Effect of Different Levels of Multienzymes on Immune Response, Blood Hematology and Biochemistry, Antioxidants Status and Organs Histology of Broiler Chicks Fed Standard and Low-Density Diets

et al. 2020

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This study was executed to investigate the effect of supplementing three multienzyme levels (0, 0. 1, and 0.2%) with two types of diet [standard diet (SD) vs. low-density diet (LDD)] on immune response, blood hematology and biochemistry, antioxidant status, and organ histology of broilers during 1-38 days of age. A total of 216 unsexed 1-day-old Arbor Acres broiler chicks were randomly distributed, on a factorial design (2 × 3), to six treatments each with six replicates. There were six chicks per replicate. Results showed that LDD significantly decreased body weight gain (BWG) of broilers, but did not affect the European Production Efficiency Index (EPEI). Addition of multienzymes at both levels (0.1 and 0.2%) significantly increased BWG and improved EPEI, compared to the control diet. Alanine aminotransferase (ALT), aspirate aminotransferase (AST), malondialdehyde (MDA), lymphocyte, lymphocyte transformation test (LTT), and phagocyte activity (PA) were significantly higher for LDD than the SD, but eosinophil was lower. Supplementation of multienzymes significantly decreased ALT, AST, and MDA, compared to the control group, but increased packed cell volume (PCV), hemoglobin (Hgb), lymphocytes, and monocytes. Immune organs, such as spleen, thymus, and the bursa of Fabricius were significantly increased with multienzyme supplementation. It could be concluded that multienzyme supplementation at either 0.1 or 0.2% to SD or LDD improved EPEI and immune status of broiler chicks.

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Section: Discussionmentioning

confidence: 99%

Effect of Different Levels of Multienzymes on Immune Response, Blood Hematology and Biochemistry, Antioxidants Status and Organs Histology of Broiler Chicks Fed Standard and Low-Density Diets

et al. 2020

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“…17 Finally, the anti-inflammatory effect of GSK3 inhibition on the kidney might be partially mediated by the modification of systemic inflammatory responses, because GSK3 also plays an important in this process (an overview is in ref. 98). …”

Section: Gsk3 Inhibition Reduces Inflammatory Responses By Regulatingmentioning

confidence: 99%

Lithium in the Kidney: Friend and Foe?

Alsady

Baumgarten²,

Deen

et al. 2015

JASN

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Trace amounts of lithium are essential for our physical and mental health, and administration of lithium has improved the quality of life of millions of patients with bipolar disorder for .60 years. However, in a substantial number of patients with bipolar disorder, long-term lithium therapy comes at the cost of severe renal side effects, including nephrogenic diabetes insipidus and rarely, ESRD. Although the mechanisms underlying the lithium-induced renal pathologies are becoming clearer, several recent animal studies revealed that short-term administration of lower amounts of lithium prevents different forms of experimental AKI. In this review, we discuss the knowledge of the pathologic and therapeutic effects of lithium in the kidney. Furthermore, we discuss the underlying mechanisms of these seemingly paradoxical effects of lithium, in which fine-tuned regulation of glycogen synthase kinase type 3, a prime target for lithium, seems to be key. The new discoveries regarding the protective effect of lithium against AKI in rodents call for follow-up studies in humans and suggest that long-term therapy with low lithium concentrations could be beneficial in CKD.

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“…These pathways have been implicated in previous BD transcriptome studies 13,14,16,23,26 and are known targets of lithium 48, 54 . The elevated levels of neutrophil proportions we observed is in line with lithium-induced neutrophilia, which has been described since the medication’s early use in psychiatry 54 . Lithium is thought to induce neutrophilia through a complex pathway involving GSK3 and immune-related transcription factors and genes 55 .…”

Section: Discussionmentioning

confidence: 82%

Whole blood transcriptome analysis in bipolar disorder reveals strong lithium effect

Krebs

Ori

Vreeker

et al. 2018

Preprint

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23Bipolar disorder (BD) is a highly heritable mood disorder with complex genetic architecture and 24 poorly understood etiology. We performed a whole blood transcriptome analysis in a BD case-25 control sample (Nsubjects = 480) by RNA sequencing. While we observed widespread differential 26 gene expression patterns between affected and unaffected individuals, these effects were largely 27 linked to lithium treatment at the time of blood draw (FDR < 0.05, Ngenes = 976) rather than BD 28 diagnosis itself (FDR < 0.05, Ngenes = 6). These lithium-associated genes were enriched for cell 29 signaling and immune response functional annotations, among others, and were associated with 30 neutrophil cell-type proportions, which were elevated in lithium users. Neither genes with altered 31 expression in cases nor in lithium users were enriched for BD, schizophrenia, and depression 32 genetic risk based on information from genome-wide association studies, nor was gene 33 expression associated with polygenic risk scores for BD. Our findings suggest that BD is 34 associated with minimal changes in whole blood gene expression independent of medication use 35 but underline the importance of accounting for medication use and cell type heterogeneity in 36 psychiatric transcriptomic studies. The results of our study add to mounting evidence of lithium's 37 cell signaling and immune-related mechanisms. 38 39 strategy for uncovering disease mechanisms. Many such studies have been carried out for BD, 48and in Table 1 we present a summary that reveals a lack of consistency between findings likely 49 owing to clinical heterogeneity, differing study designs, and the low numbers of samples 50 investigated (N ≤ 62 BD subjects) . Moreover, there are many potential confounds that impact 51 gene expression, including medication. 52 Therefore, to explore gene expression changes associated with BD, we generated RNA 53 sequencing data from peripheral whole blood collected in a large, well-characterized case-control 54 cohort from The Netherlands. We examined gene expression differences between groups both at 55 the individual gene level and at the level of gene co-expression. Upon correction for technical and 56 biological variables including the use of lithium, the most widely used prescription drug in our 57 cohort, gene expression differences between subjects with BD and controls were minor. 58Differences in subjects being treated with lithium compared to those who are not, however, were 59 widespread. These differences were partially but not entirely explained by differences in cell-type 60 composition, driven by elevated neutrophil proportions in lithium users. The lithium-associated 61 changes in gene expression were independent of psychiatric genetic risk, though. Our results 62 suggest nominal BD-related gene expression effects in blood but numerous effects related to 63 lithium treatment. This work highlights the importance of accounting for medication use in 64 psychiatric transcriptomic studies and provides insight into lithium's mole...

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Review of lithium effects on immune cells

Cited by 37 publications

References 74 publications

Effect of Different Levels of Multienzymes on Immune Response, Blood Hematology and Biochemistry, Antioxidants Status and Organs Histology of Broiler Chicks Fed Standard and Low-Density Diets

Effect of Different Levels of Multienzymes on Immune Response, Blood Hematology and Biochemistry, Antioxidants Status and Organs Histology of Broiler Chicks Fed Standard and Low-Density Diets

Lithium in the Kidney: Friend and Foe?

Whole blood transcriptome analysis in bipolar disorder reveals strong lithium effect

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