Cytokine storm and targeted therapy in hemophagocytic lymphohistiocytosis

Zhang, Hanqi; Yang, Siwei; Fu, Yicheng; Chen, Ming-Cong; Yang, Chenghao; Yang, Minghua; Liu, Xiaodan; He, Qingnan; Jiang, Hua; Zhao, Mingyi

doi:10.1007/s12026-022-09285-w

Cited by 13 publications

(12 citation statements)

References 112 publications

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“…Viral infections, particularly EBV, are the most common trigger of HLH; however, infections from Leishmania spp, Cryptococcus spp, Mycobacterium tuberculosis , and Anaplasma have been observed [ 1 , 18–20 ]. With symptoms of fever and hepatitis overlapping with severe anaplasmosis, HLH occurs due to dysregulation of innate and adaptive immune responses and a proinflammatory state with elevated cytokine levels as seen in a cytokine storm [ 21 , 22 ]. HLH is usually treated with immunosuppressive therapies [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Anaplasmosis-Induced Hemophagocytic Lymphohistiocytosis: A Case Report and Review of the Literature

Scribner

Lamyaithong

et al. 2023

Open Forum Infectious Diseases

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Section: Discussionmentioning

confidence: 99%

Anaplasmosis-Induced Hemophagocytic Lymphohistiocytosis: A Case Report and Review of the Literature

Scribner

Lamyaithong

et al. 2023

Open Forum Infectious Diseases

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“…This results in haemophagocytosis of host platelets, leucocytes and red blood cells. In addition, the (over)activation of the cytotoxic T lymphocytes, NK cells, and macrophages induces a cytokine storm in which large amounts of cytokines including IL-1β, IL-6, IL-18, IFN-γ, and TNF-α are produced and released ( 48 ). This cytokine storm is thought to cause multi-organ failure in HLH ( 49 ).…”

Section: Discussionmentioning

confidence: 99%

Did variants in inborn errors of immunity genes contribute to the extinction of Neanderthals?

Zhou

Swagemakers

Lourens

et al. 2022

Preprint

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Neanderthals were a species of archaic human that became extinct around 40,000 years ago. Modern humans have inherited 1-6% of Neanderthal DNA as a result of interbreeding with the Neanderthals. These inherited Neanderthal genes have paradoxical influences, while some can provide protection to viral infections, some others are associated with autoimmune/auto-inflammatory diseases. We hypothesized that genetic variants with strong detrimental effects on the function of the immune system could potentially contributed to the extinction of the Neanderthal population. In modern humans more than 450 genes are associated with inborn errors of immunity (IEI). We used the publically available genome information from a Neanderthal from the Altai mountains and filtered for potentially damaging variants that were present in genes associated with IEI, and checked whether these variants were present in the genomes of the Denisovan, Vindija and Chagyrskaya Neanderthals. We identified 24 homozygous variants and 15 heterozygous variants in IEI-related genes in the Altai Neanderthal. Interestingly, two homozygous variants in the UNC13D gene and one variant in the MOGS gene were present in all archaic genomes. Defects in the UNC13D gene are known to cause a severe and often fatal disease called hemophagocytic lymphohistiocystosis (HLH). One of these variants p.(Asn943Ser) has been reported in patients with HLH. Variants in MOGS are associated with glycosylation defects in the immune system affecting the susceptibility for infections. So, although we do not know exactly the functional impact yet, these three variants could have resulted in an increased susceptibility to severe diseases, and may have contributed to the extinction of Neanderthals after exposure to specific infections.

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“…Therefore, cytokine targeting therapy has been focused on as a novel therapy for various diseases: cancer (Berraondo et al, 2019;Dougan et al, 2018), heart failure (Hanna & Frangogiannis, 2020), rheumatoid arthritis (RA) (Noack & Miossec, 2017), and lymphohistiocytosis (H. Q. Zhang et al, 2022).…”

Section: Cytokinesmentioning

confidence: 99%

“…Cytokines are important molecules in inflammatory response and are recently focused as the therapeutic target for various diseases (Fajgenbaum & June, 2020; Lippitz, 2013; Propper & Balkwill, 2022). Therefore, cytokine targeting therapy has been focused on as a novel therapy for various diseases: cancer (Berraondo et al, 2019; Dougan et al, 2018), heart failure (Hanna & Frangogiannis, 2020), rheumatoid arthritis (RA) (Noack & Miossec, 2017), and lymphohistiocytosis (H. Q. Zhang et al, 2022).…”

Section: Target Moleculesmentioning

confidence: 99%

The anti‐inflammatory effect of metformin: The molecular targets

Sakata

2024

Genes to Cells

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Metformin is an anti‐diabetic drug. Metformin mainly inhibits gluconeogenesis in the liver and reduces blood sugar. In addition to the anti‐diabetic effects, many studies have revealed that metformin has anti‐inflammatory effects. Various molecules were suggested to be the target of the metformin's anti‐inflammatory effects. However, the conclusion is not clear. Metformin is related to a number of molecules and the identification of the main target in anti‐inflammatory effects leads to the understanding of inflammation and metformin. In this article, I discuss each suggested molecule, involved mechanisms, and their relationship with various diseases.

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Cytokine storm and targeted therapy in hemophagocytic lymphohistiocytosis

Cited by 13 publications

References 112 publications

Anaplasmosis-Induced Hemophagocytic Lymphohistiocytosis: A Case Report and Review of the Literature

Anaplasmosis-Induced Hemophagocytic Lymphohistiocytosis: A Case Report and Review of the Literature

Did variants in inborn errors of immunity genes contribute to the extinction of Neanderthals?

The anti‐inflammatory effect of metformin: The molecular targets

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