Alzheimer's disease (AD) is one of the most prevalent forms of neurodegenerative disorders. Previously, we have shown that in vivo administration of an IL-17 neutralizing antibody (IL-17Ab) rescues amyloid-β-induced neuro-inflammation and memory impairment, demonstrating the pivotal role of IL-17 in AD-derived cognitive deficit. Recently, AD has been recognized as a more intriguing pathology affecting vascular network and platelet function. However, not much is known about peripheral vascular inflammation and how pro-inflammatory circulating cells/mediators could affect peripheral vessels' function. This study aimed to evaluate whether IL-17Ab treatment could also impact peripheral AD features, such as systemic inflammation, peripheral vascular dysfunction, and related pro-thrombotic state in a non-genetic mouse model of AD. Mice were injected intracerebroventricularly with Aβ1-42 peptide (3μg/3μl). To evaluate the systemic/peripheral protective profile of IL-17Ab, we used an intranasal administration of IL-17Ab (1μg/10μl) at 5, 12, and 19 days after Aβ1-42 injection. Circulating Th17/Treg cells and related cyto-chemokines, haematological parameters, vascular/endothelial reactivity, platelets and coagulation function in mice were evaluated. IL-17Ab treatment ameliorates the systemic/peripheral inflammation, immunological perturbance, vascular/endothelial impairment and pro-thrombotic state, suggesting a key role for this cytokine in fostering inflammatory processes that characterize the multifaced aspects of AD.

Interleukin-17 (IL-17) triggers systemic inflammation, peripheral vascular dysfunction, and related prothrombotic state in a mouse model of Alzheimer's disease / Vellecco, Valentina; Saviano, Anella; Raucci, Federica; Casillo, Gian Marco; Mansour, Adel Abo; Panza, Elisabetta; Mitidieri, Emma; Femminella, Grazia Daniela; Ferrara, Nicola; Cirino, Giuseppe; Sorrentino, Raffaella; Iqbal, Asif Jilani; di Villa Bianca, Roberta d'Emmanuele; Bucci, Mariarosaria; Maione, Francesco. - In: PHARMACOLOGICAL RESEARCH. - ISSN 1043-6618. - 187:(2023), p. 106595. [10.1016/j.phrs.2022.106595]

Interleukin-17 (IL-17) triggers systemic inflammation, peripheral vascular dysfunction, and related prothrombotic state in a mouse model of Alzheimer's disease

Vellecco, Valentina;Saviano, Anella;Raucci, Federica;Casillo, Gian Marco;Panza, Elisabetta;Mitidieri, Emma;Femminella, Grazia Daniela;Ferrara, Nicola;Cirino, Giuseppe;Sorrentino, Raffaella;di Villa Bianca, Roberta d'Emmanuele;Bucci, Mariarosaria
;
Maione, Francesco
2023

Abstract

Alzheimer's disease (AD) is one of the most prevalent forms of neurodegenerative disorders. Previously, we have shown that in vivo administration of an IL-17 neutralizing antibody (IL-17Ab) rescues amyloid-β-induced neuro-inflammation and memory impairment, demonstrating the pivotal role of IL-17 in AD-derived cognitive deficit. Recently, AD has been recognized as a more intriguing pathology affecting vascular network and platelet function. However, not much is known about peripheral vascular inflammation and how pro-inflammatory circulating cells/mediators could affect peripheral vessels' function. This study aimed to evaluate whether IL-17Ab treatment could also impact peripheral AD features, such as systemic inflammation, peripheral vascular dysfunction, and related pro-thrombotic state in a non-genetic mouse model of AD. Mice were injected intracerebroventricularly with Aβ1-42 peptide (3μg/3μl). To evaluate the systemic/peripheral protective profile of IL-17Ab, we used an intranasal administration of IL-17Ab (1μg/10μl) at 5, 12, and 19 days after Aβ1-42 injection. Circulating Th17/Treg cells and related cyto-chemokines, haematological parameters, vascular/endothelial reactivity, platelets and coagulation function in mice were evaluated. IL-17Ab treatment ameliorates the systemic/peripheral inflammation, immunological perturbance, vascular/endothelial impairment and pro-thrombotic state, suggesting a key role for this cytokine in fostering inflammatory processes that characterize the multifaced aspects of AD.
2023
Interleukin-17 (IL-17) triggers systemic inflammation, peripheral vascular dysfunction, and related prothrombotic state in a mouse model of Alzheimer's disease / Vellecco, Valentina; Saviano, Anella; Raucci, Federica; Casillo, Gian Marco; Mansour, Adel Abo; Panza, Elisabetta; Mitidieri, Emma; Femminella, Grazia Daniela; Ferrara, Nicola; Cirino, Giuseppe; Sorrentino, Raffaella; Iqbal, Asif Jilani; di Villa Bianca, Roberta d'Emmanuele; Bucci, Mariarosaria; Maione, Francesco. - In: PHARMACOLOGICAL RESEARCH. - ISSN 1043-6618. - 187:(2023), p. 106595. [10.1016/j.phrs.2022.106595]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/903280
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