Drug-Cytokine Interactions

Goralski, Kerry B.; Ladda, Matthew; McNeil, Jenna O.

doi:10.1007/978-3-319-72422-5_5

Cited by 5 publications

(12 citation statements)

References 227 publications

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“…Anti-cytokine therapy has been widely used to treat immune diseases in the last decade [40]. Such approved drugs include inhibitors of TNF-α (e.g., etanercept and adalimumab), IL-6 (e.g., tocilizumab), and IL-1β (e.g., canakinumab) signaling for immune diseases such as rheumatoid arthritis and Crohn's disease [41]. Surprisingly, proinflammatory cytokines are also found to be highly expressed in major depression disorder (MDD) patients [42]; in particular, TNF-α stimulates the development of MDD by changing the function and structure of the brain [43].…”

Section: Discussionmentioning

confidence: 99%

Exopolysaccharide Isolated from Lactobacillus plantarum L-14 Has Anti-Inflammatory Effects via the Toll-Like Receptor 4 Pathway in LPS-Induced RAW 264.7 Cells

Kwon

Lee²,

Park

et al. 2020

IJMS

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Inflammation is a biological response of the immune system to defend the body from negative stimulation. However, the excessive inflammatory response can damage host tissues and pose serious threats. Exopolysaccharide (EPS), one of the postbiotics, is secreted from lactic acid bacteria. Although many studies have described the beneficial effects of EPS, such as its anti-inflammatory and anti-oxidant effects, its underlying mechanisms have remained to be poorly understood. Thus, we identified that EPS obtained from Lactobacillus plantarum L-14 was a homogeneous polysaccharide primarily comprised of glucose. To examine these anti-inflammatory effects, an inflammatory response was induced by lipopolysaccharide (LPS) administration to mouse macrophage RAW 264.7 cells that were pretreated with EPS. The anti-inflammatory effects of EPS were identified by analyzing the changes within inflammatory markers at the molecular level. We demonstrate here that EPS suppressed proinflammatory mediators, such as cyclooxygenase-2, interleukin-6, tumor necrosis factor-α, and interleukin-1β, and downregulated the expression of an inducible nitric oxide synthase known to lead to oxidative stress. It was also confirmed that EPS had anti-inflammatory effects by blocking the interaction of LPS with Toll-like receptor 4 (TLR4), as demonstrated by using the known TLR4 inhibitor TAK-242. In addition, we found that EPS itself could suppress the expression of TLR4. Consequently, our data suggest that EPS can be a potential target for the development of natural product-derived medicine for treating inflammatory diseases related to TLR4.

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Section: Discussionmentioning

confidence: 99%

Exopolysaccharide Isolated from Lactobacillus plantarum L-14 Has Anti-Inflammatory Effects via the Toll-Like Receptor 4 Pathway in LPS-Induced RAW 264.7 Cells

Kwon

Lee²,

Park

et al. 2020

IJMS

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“…As of now, it appears that the degree of inflammation positively correlates to interaction potential; therefore significant drug-cytokine interactions are mostly observed during acute inflammation with immune response or induction/discontinuation of cytokine-therapies ( Zhou and Sharma, 2016 ). By monitoring both cytokine and affected drug levels, our case demonstrated drug-cytokine interaction was of significant clinical importance—cytokines and anti-cytokine biologicals can affect therapeutic effects or toxicities of co-medications, which required close monitoring during clinical practice, especially for patients with infection, inflammation or cancer ( Morgan et al., 2008 ; Veringa et al., 2017 ; Goralski et al., 2018 ).…”

Section: Discussionmentioning

confidence: 98%

“…While therapeutic proteins are increasingly approved and prescribed over the world, our understanding of drug interactions associated with them is still premature and sometimes controversial. Preclinical studies revealed that exposure to cytokines such as IL-1, IL-2, IL-6, and TNF-alpha can reduce hepatic cytochrome P450 metabolism through transcriptional regulation of CYP synthesis ( Goralski et al., 2018 ). In patients receiving biologicals, the resolution of inflammation by anti-cytokine therapies can therefore increase drug clearance, due to reversal of the down-regulation and induction of the suppressed enzymes ( Morgan, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

“…It is a fusion protein consists of two p75 TNF receptors bound to the fragment crystallizable region of immunoglobulin G. No specific drug interaction studies were conducted with etanercept during its clinical development, as it was presumed that etanercept would be metabolized as peptides and amino acids rather than as a CYP450 substrate (Zhou, 2005). However, later studies showed that anti-cytokine therapies can alter drug dispositions through "drug-cytokine interaction" (Goralski et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…Cytokines, such as interleukins (IL), interferons, and TNFs are hormone-like glycoproteins that regulate human immunologic responses as mediators ( Goralski et al., 2018 ). The term “drug-cytokine interaction” is used to describe how cytokines interact with drug-metabolizing enzymes or drug transporters and therefore influence drug dispositions.…”

Section: Introductionmentioning

confidence: 99%

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Probable Drug Interaction Between Etanercept and Cyclosporine Resulting in Clinically Unexpected Low Trough Concentrations: First Case Report

Wen

Chen

et al. 2020

Front. Pharmacol.

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Preclinical studies have shown that anti-cytokine therapies could alter drug dispositions through affecting cytochrome P450 synthesis; however, evidence and case reports evaluating clinical relevance of this interaction are scarce. This is the first reported case of interaction between cyclosporine (CsA) and etanercept in a 42-year-old male patient with ankylosing spondylitis and immunoglobulin A nephropathy in whom cytokine levels were monitored both before and after CsA initiation. The initiation of etanercept led to at least 2.5-folds increase in total clearance of CsA. After comprehensive assessment and stepwise exclusion of alternative causes, it was considered that inflammation resolution with etanercept administration has highly induced clearance of CsA, probably mediated by interleukin-2. The case has shown that co-administration of CsA and anti-cytokine therapies such as etanercept needs close monitoring of trough levels. Physicians and pharmacists should be aware of similar interactions especially when the biological therapy is initiated or discontinued and for patients undergoing acute inflammation phase. Monitoring cytokine levels should be considered when drug-cytokine interaction is suspected.

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Pharmacokinetics under the COVID‐19 storm

Reddy

El‐Khateeb

et al. 2021

Brit J Clinical Pharma

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 cancer, cirrhosis, and rheumatoid arthritis. Cytokine storms are known to perturb the expression of CYP enzymes, conjugative enzymes, and transporters.  Clinically observed pharmacokinetic data and the effect of race on repurposed COVID-19 drugs in geriatric COVID-19 patients are limited.  There is some knowledge of the effect of intrinsic and extrinsic factors on the disposition of repurposed COVID-19 drugs, but dosing recommendations for patients with a cytokine storm are lacking What this study adds:  A comprehensive summary of ADME, DDI, Adverse Events (AEs) and simulated lung exposure for COVID-19 repurposed drugs  Verified PBPK models that predict changes in drug exposure in various clinical scenarios, guiding dosing information where it is not possible to obtain clinical data , particularly given the COVID-19 pandemic  Simulated plasma and lung tissue exposure of drugs to justify broader recruitment criteria for patients and assess the relevant potency values from in vitro studies for SARS-CoV-2

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Drug-Cytokine Interactions

Cited by 5 publications

References 227 publications

Exopolysaccharide Isolated from Lactobacillus plantarum L-14 Has Anti-Inflammatory Effects via the Toll-Like Receptor 4 Pathway in LPS-Induced RAW 264.7 Cells

Exopolysaccharide Isolated from Lactobacillus plantarum L-14 Has Anti-Inflammatory Effects via the Toll-Like Receptor 4 Pathway in LPS-Induced RAW 264.7 Cells

Probable Drug Interaction Between Etanercept and Cyclosporine Resulting in Clinically Unexpected Low Trough Concentrations: First Case Report

Pharmacokinetics under the COVID‐19 storm

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