A ferret model of immunosuppression induced with dexamethasone

Hundakova, Anna; Levá, Lenka; Toman, M.; Knotek, Z.

doi:10.1016/j.vetimm.2021.110362

Cited by 3 publications

(3 citation statements)

References 51 publications

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“…In this study, we carried out experiments using two FDA-approved drugs, aspirin (acetylsalicylic acid, ASA) and dexamethasone, which have been reported to yield immunosuppressive effects in several animal models including humans [11][12][13][14][15][16][17][18]. We ought to examine whether a similar immunoinhibitory effect can be observed in our D. melanogaster model system.…”

Section: Introductionmentioning

confidence: 99%

Proof-of-Concept Preclinical Use of Drosophila melanogaster in the Initial Screening of Immunomodulators

et al. 2022

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Drug discovery is a complex process, and the use of a comprehensive approach is deemed necessary to discover new chemical entities with novel mechanisms of action. This research was carried out to determine whether Drosophila melanogaster can serve as an appropriate model organism in the initial screening of drug candidates with immunomodulatory activities. To test this, we performed phenotypic assay and molecular analysis to investigate the immunomodulatory activities of aspirin, dexamethasone, curcumin, and epigallocatechin gallate (EGCG), that have been reported to yield such effects in the mammalian model system. In vivo survival analysis demonstrated that all drugs/compounds were relatively safe at the tested concentrations. In the infection assay, curcumin and EGCG showed a protective signature to bacterial infection in flies lacking Toll-mediated immune responses. Furthermore, dexamethasone and aspirin, drugs with immunosuppressive activity, could improve the survival of PGRP-LBΔ mutant flies with hyperactivated immune system. These phenotypes were supported by RT-qPCR-based molecular analysis, revealing that drugs/compounds used in this study could modulate the expression level of genes related to the immune system. In conclusion, while curcumin and EGCG could promote the improvement of fly survival against infection, aspirin and dexamethasone were able to suppress overactivation of immune responses in D. melanogaster. These results are in line with the ones observed in the mammalian model system, further emphasizing the notion that flies would serve as a prospective model organism in the initial screening of drug candidates for their immunomodulatory activities prior to further checking in the mammalian animal models. In the end, this will reduce the use of mammalian animal models for preliminary experiments in an effort to discover/repurpose drugs with immunomodulatory activity.

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Section: Introductionmentioning

confidence: 99%

Proof-of-Concept Preclinical Use of Drosophila melanogaster in the Initial Screening of Immunomodulators

et al. 2022

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“…Another advantage of this species are the cheek pouches which are considered an immune desert due to the lack of lymphatic drainage pathways offering the potential of long-term transplantation of foreign material, such as patient derived tumor tissue without immune rejection ( 40 ). Secondly, ferrets can be suitable models as they have a particularly high cancer prevalence, which could give insights into the biological development of cancer, and have shown useful in immunology studies ( 41 , 42 ). Higher animal models such as canines and swine are also available.…”

Section: Limited Relevant Preclinical Research Could Relate To Failin...mentioning

confidence: 99%

Preclinical studies performed in appropriate models could help identify optimal timing of combined chemotherapy and immunotherapy

Berckmans,

Ceusters,

Vankerckhoven

et al. 2023

Front. Immunol.

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Immune checkpoint inhibitors (ICI) have been revolutionary in the field of cancer therapy. However, their success is limited to specific indications and cancer types. Recently, the combination treatment of ICI and chemotherapy has gained more attention to overcome this limitation. Unfortunately, many clinical trials testing these combinations have provided limited success. This can partly be attributed to an inadequate choice of preclinical models and the lack of scientific rationale to select the most effective immune-oncological combination. In this review, we have analyzed the existing preclinical evidence on this topic, which is only limitedly available. Furthermore, this preclinical data indicates that besides the selection of a specific drug and dose, also the sequence or order of the combination treatment influences the study outcome. Therefore, we conclude that the success of clinical combination trials could be enhanced by improving the preclinical set up, in order to identify the optimal treatment combination and schedule to enhance the anti-tumor immunity.

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“…Dexamethasone can cause an immunosuppressive state in animals, and it was selected as an immunosuppressive drug in this test. In experiments studying animal models of dexamethasone-induced immunosuppression pathology, more attention has been paid to changes in leukocytes and immune cells, and a lack of focus on clinical signs such as body weight ( Lo et al, 2005 ; Harada et al, 2011 ; Hundakova et al, 2022 ). Immunosuppression led to atrophy of the thymus and the bursin, organ function was affected, and organ indexes showed a significant decrease after modeling, whereas the spleen showed no difference.…”

Section: Introductionmentioning

confidence: 99%

Effect of Echinacea on gut microbiota of immunosuppressed ducks

Lin

Zhi

et al. 2023

Front. Microbiol.

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IntroductionImmunosuppression puts animals in a susceptible state and disrupts the balance of intestinal flora, which can increase the risk of disease and cause serious harm to the farm. Echinacea can exert its immunomodulatory effect in various ways, but its influence on intestinal flora is unclear.MethodsTherefore, we investigated the effect of Echinacea extract (EE) on gut microbiota in immunosuppressed ducks by 16s-RNA sequencing in this experiment.ResultsThe results showed that EE significantly improved the weight gain of immunosuppressed ducks (p<0.001). It also increased the immune organ index (p<0.01) and upregulated the levels of TNF-α and IFN-γ (p<0.05) as well as IL-2 in the serum. The lesions of the bursa were evident compared to the spleen and thymus. After treatment in the EE group, the lymphocyte count of the bursa returned to healthy levels and the lesions were significantly improved. The diversity analysis showed that neither of the alpha-diversity indices showed a significant difference (p>0.05). However, the EE group had a trend closer to the healthy group compared to the M group. β-diversity analysis revealed a high degree of sample separation between the healthy and immunosuppressed groups. The sequencing result showed a significantly higher relative abundance of Prevotella and Prevotella_UCG_001 in the dexamethasone-treated group, which could be potential biomarkers of dexamethasone-induced immunosuppression. EE increased the relative abundance of Akkermansia, Bacteroides, and Alistipes and significantly decreased the relative abundance of Megamonas, Streptococcus, and Enterococcus (p<0.05).ConclusionThe results showed that Echinacea extract improves the development of immunosuppressed ducks and modulates intestinal immune function by increasing the abundance of beneficial bacterial genera in the intestine.

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A ferret model of immunosuppression induced with dexamethasone

Cited by 3 publications

References 51 publications

Proof-of-Concept Preclinical Use of Drosophila melanogaster in the Initial Screening of Immunomodulators

Proof-of-Concept Preclinical Use of Drosophila melanogaster in the Initial Screening of Immunomodulators

Preclinical studies performed in appropriate models could help identify optimal timing of combined chemotherapy and immunotherapy

Effect of Echinacea on gut microbiota of immunosuppressed ducks

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