Cytokine Detection and Modulation in Acute Graft <i>vs</i>. Host Disease in Mice

Knulst, André C.; Tibbe, G. J. M.; Bril-Bazuin, C.; Breedland, E. G.; Oudenaren, A. Van; Benner, R.; Savelkoul, H.F.J.

doi:10.1155/s0962935194000062

Cited by 3 publications

(4 citation statements)

References 10 publications

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“…It has been revealed that IFN‐γ is responsible for Th1‐type responses such as acute GVHD, whereas IL‐4 is related to Th2‐type responses such as chronic GVHD (35, 36). Elevated serum IFN‐γ level was observed in the control IgG‐treated BMS recipient mice on day seven consisting with the previous report (37), and anti‐B7RP‐1 mAb treatment significantly reduced serum IFN‐γ (p < 0.05) (Table 1). IFN‐γ was not detected in the sera of recipients given TCD‐BM at any time points and in the sera of BMS recipients on day 14, 21, and 28.…”

Section: Resultssupporting

confidence: 88%

Contribution of B7RP-1/ICOS co-stimulation to lethal acute GVHD

Fujimura¹,

Takeda²,

Kaduka

et al. 2010

Pediatric Transplantation

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Co-stimulatory molecules expressed on T cells critically regulate donor T-cell activation and are implicated in acute GVHD after allogeneic BMT. We here investigated the role of interaction between B7-related protein-1 (B7RP-1) and ICOS in murine acute GVHD model that received T cell-depleted BM cells and splenocytes. Administration of blocking anti-B7RP-1 mAb significantly reduced the lethality and symptoms in acute GVHD. A significant hypo-responsiveness of splenocytes to host alloantigen was observed in the recipient mice treated with anti-B7RP-1 mAb. Moreover, acute GVHD was significantly reduced in the recipients of T cells composed of ICOS-deficient CD8 T cells and WT CD4 T cells compared with that in the recipients of T cells composed of WT CD8 T cells and ICOS-deficient CD4 T cells. These results suggested that B7RP-1/ICOS co-stimulatory signal plays a role in the activation of alloantigen-reactive donor T cells, particularly in CD8 T cells, in murine acute GVHD model, and that the blockade of B7RP-1/ICOS interaction may be useful for selectively manipulating allo-reactive T cells in the recipients with acute GVHD.

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Section: Resultssupporting

confidence: 88%

Contribution of B7RP-1/ICOS co-stimulation to lethal acute GVHD

Fujimura¹,

Takeda²,

Kaduka

et al. 2010

Pediatric Transplantation

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“…Proinflammatory cytokines are critical in the process of inflammation, and the increased production of TNF-α, IL-6, IL-1β and IFN-γ has previously been reported to be associated with autoimmune cardiac diseases (26)(27)(28). In the current study, injection with LPS resulted in marked intrahepatic increases of TNF-α, IL-6, IL-1β and IFN-γ, which was consistent with previous reports (29). Subsequent LY294002 treatment clearly inhibited the serum protein levels of TNF-α, IL-6, IL-1β and IFN-γ; the T cell-produced cytokines in LPS-injected mice.…”

Section: Discussionsupporting

confidence: 93%

LY294002 prevents lipopolysaccharide-induced hepatitis in a murine model by suppressing IκB phosphorylation

Chen

Liu

Lei

et al. 2015

Molecular Medicine Reports

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Although fulminant hepatitis represents a ubiquitous human health problem, there is a lack of effective therapeutic strategies that have few side‑effects and the precise mechanisms underlying fulminant hepatitis are not fully understood. Phosphoinositide 3‑kinase (PI3K) is a pivotal kinase known to regulate inflammatory responses in hepatic diseases. Although previous research indicates that PI3K is involved in cardiac diseases, including myocardial infarction, it currently remains unclear whether the inhibition of PI3K is essential for ameliorating the severity of lipopolysaccharide (LPS)‑induced hepatitis. The aim of the present study was to investigate whether pharmacological blockade of PI3K ameliorates the development of LPS‑induced murine acute hepatic injury. A murine model of LPS‑induced acute hepatic injury was used to investigate the therapeutic effect of the pan‑PI3K inhibitor, LY294002 on murine fulminant hepatitis and to investigate potential underlying mechanisms. The current report presents the in vivo role of LY294002 in protecting the mice from fulminant hepatitis. LY294002 was observed to exert significant protective effects on the liver by reducing the activities of alanine aminotransferase and aspartate aminotransferase, as well as by improving the histological architecture of the liver. In LPS‑induced hepatitis, treatment with LY294002 clearly inhibited intrahepatic synthesis of various disease‑relevant proinflammatory cytokines, including tumor necrosis factor‑α, interleukin (IL)‑6, IL‑1β and interferon‑γ. Furthermore, LY294002 was observed to significantly inhibit IκB phosphorylation in LPS‑injured mouse liver samples. Therefore, LY294002 may protect the liver from LPS‑induced injury by inhibition of the IκB‑nuclear factor κ‑light‑chain‑enhancer of activated B cell dependent signaling pathway. Thus, the current report provides evidence that LY294002 exerts potent effects against LPS‑induced hepatic injury, indicating its potential therapeutic value for the treatment of acute hepatitis.

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“…They were randomly chosen from the Evax database. The median age was 50 years (40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53), significantly higher than that of patients (p < 0.001). The sex ratio was 0.82 (14 men, 17 women) (p = 0.366 when compared to patients).…”

Section: Clinical Tolerance Of Vaccinationmentioning

confidence: 90%

“…As expected, IL-2 levels were correlated with IFN-γ levels, even though they were significantly higher in patients compared to controls. The high level of IL-2 in the patients cannot be explained by the particular contexts of the patients (ASCT and GVHD) since studies have proven that the levels of IL-2 were low to undetectable in this group of patients [ 40 ]. The difference could be attributed to the age difference between the groups.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and Tolerance of BNT162b2 mRNA Vaccine in Allogeneic Hematopoietic Stem Cell Transplant Patients

Ben Khlil,

Zamali,

Belloumi

et al. 2024

Vaccines

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Background: Allogeneic hematopoietic stem cell transplantation (ASCT) induces acquired immunodeficiency, potentially altering vaccine response. Herein, we aimed to explore the clinical tolerance and the humoral and cellular immune responses following anti-SARS-CoV-2 vaccination in ASCT recipients. Methods: A prospective, non-randomized, controlled study that involved 43 ASCT subjects and 31 healthy controls. Humoral response was investigated using the Elecsys® test anti-SARS-CoV-2. Cellular response was assessed using the QFN® SARS-CoV-2 test. The lymphocyte cytokine profile was tested using the LEGENDplex™ HU Th Cytokine Panel Kit (12-plex). Results: Adverse effects (AE) were observed in 69% of patients, encompassing pain at the injection site, fever, asthenia, or headaches. Controls presented more side effects like pain in the injection site and asthenia with no difference in the overall AE frequency. Both groups exhibited robust humoral and cellular responses. Only the vaccine transplant delay impacted the humoral response alongside a previous SARS-CoV-2 infection. Noteworthily, controls displayed a Th1 cytokine profile, while patients showed a mixed Th1/Th2 profile. Conclusions: Pfizer-BioNTech® anti-SARS-CoV-2 vaccination is well tolerated in ASCT patients, inducing robust humoral and cellular responses. Further exploration is warranted to understand the impact of a mixed cytokine profile in ASCT patients.

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Cytokine Detection and Modulation in Acute Graft vs. Host Disease in Mice

Cited by 3 publications

References 10 publications

Contribution of B7RP-1/ICOS co-stimulation to lethal acute GVHD

Contribution of B7RP-1/ICOS co-stimulation to lethal acute GVHD

LY294002 prevents lipopolysaccharide-induced hepatitis in a murine model by suppressing IκB phosphorylation

Immunogenicity and Tolerance of BNT162b2 mRNA Vaccine in Allogeneic Hematopoietic Stem Cell Transplant Patients

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