Thalidomide modulates renal inflammation induced by brain death experimental model.

Autor: Santana AC; Neurological Surgery Department, University of São Paulo, School of Medicine, São Paulo, Brazil; Organ Procurement Organization, Hospital das Clínicas, University of São Paulo, School of Medicine, São Paulo, Brazil. Electronic address: alesantana@usp.br., Andraus W; Gastroenterology Department, University of São Paulo, School of Medicine, São Paulo, Brazil., Silva FMO; Medical Science Department, Nove de Julho University, São Paulo, Brazil., Sala ACG; Medical Science Department, Nove de Julho University, São Paulo, Brazil., Schust AS; Medical Science Department, Nove de Julho University, São Paulo, Brazil., Neri LHM; Medical Science Department, Nove de Julho University, São Paulo, Brazil., Feliciano R; Medical Science Department, Nove de Julho University, São Paulo, Brazil., Pepineli R; Medical Science Department, Nove de Julho University, São Paulo, Brazil., Dellê H; Medical Science Department, Nove de Julho University, São Paulo, Brazil., Ruiz LM; Cardiopneumology Department, University of São Paulo, School of Medicine, São Paulo, Brazil., de Oliveira-Braga KA; Cardiopneumology Department, University of São Paulo, School of Medicine, São Paulo, Brazil., Nepomuceno NA; Cardiopneumology Department, University of São Paulo, School of Medicine, São Paulo, Brazil., Pêgo-Fernandes PM; Cardiopneumology Department, University of São Paulo, School of Medicine, São Paulo, Brazil., Dos Santos MJ; School of Nursing of the University of São Paulo, São Paulo, Brazil., de Moraes EL; Organ Procurement Organization, Hospital das Clínicas, University of São Paulo, School of Medicine, São Paulo, Brazil., Brasil S; Neurological Surgery Department, University of São Paulo, School of Medicine, São Paulo, Brazil., Figueiredo EG; Neurological Surgery Department, University of São Paulo, School of Medicine, São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Transplant immunology [Transpl Immunol] 2022 Dec; Vol. 75, pp. 101710. Date of Electronic Publication: 2022 Sep 10.
DOI: 10.1016/j.trim.2022.101710
Abstrakt: Background: Brain death (BD) is characterized by a complex inflammatory response, resulting in dysfunction of potentially transplantable organs. This process is modulated by cytokines, which amplify graft immunogenicity. We have investigated the inflammatory response in an animal model of BD and analyzed the effects of thalidomide, a drug with powerful immunomodulatory properties.
Methods: BD was induced in male Lewis rats. We studied three groups: Control (sham-operated rats) (n = 6), BD (rats subjected to brain death) (n = 6) and BD + Thalid (BD rats treated with one dose of thalidomide (200 mg/Kg), administered by gavage) (n = 6). Six hours after BD, serum levels of urea and creatinine, as well as systemic and renal tissue protein levels of TNF-α and IL-6, were analyzed. We also determined the mRNA expression of ET-1, and macrophage infiltration by immunohistochemistry.
Results: BD induced a striking inflammatory status, demonstrated by a significant increase of plasma cytokines: TNF-α (2.8 ± 4.3 pg/mL [BD] vs. 9.4 ± 2.8 pg/mL [Control]), and IL-6 (6219.5 ± 1380.6 pg/mL [BD] vs. 1854.7 ± 822.6 pg/mL [Control]), and in the renal tissue: TNF-α (2.5 ± 0.3 relative expression [BD] vs. 1.0 ± 0.4 relative expression [Control]; p < 0.05), and IL-6 (4.0 ± 0.4 relative expression [BD] vs. 1.0 ± 0.3 relative expression [Control]; p < 0.05). Moreover, BD increased macrophages infiltration (2.47 ± 0.07 cells/field [BD] vs. 1.20 ± 0.05 cells/field [Control]; p < 0.05), and ET-1 gene expression (2.5 ± 0.3 relative expression [BD] vs. 1.0 ± 0.2 relative expression [Control]; p < 0.05). In addition, we have observed deterioration in renal function, characterized by an increase of urea (194.7 ± 25.0 mg/dL [BD] vs. 108.0 ± 14.2 mg/dL [Control]; p < 0.05) and creatinine (1.4 ± 0.04 mg/dL [BD] vs. 1.0 ± 0.07 mg/dL [Control]; p < 0.05) levels. Thalidomide administration significantly reduced plasma cytokines: TNF-α (5.1 ± 1.4 pg/mL [BD + Thalid] vs. BD; p < 0.05), and IL-6 (1056.5 ± 488.3 pg/mL [BD + Thalid] vs. BD; p < 0.05), as well as in the renal tissue: TNF-α (1.5 ± 0.2 relative expression [BD + Thalid] vs. BD; p < 0.05), and IL-6 (2.1 ± 0.3 relative expression [BD + Thalid] vs. BD; p < 0.05). Thalidomide treatment also induced a significant decrease in the expression of ET-1 (1.4 ± 0.3 relative expression [BD + Thalid] vs. BD; p < 0.05), and macrophages infiltration (1.17 ± 0.06 cells/field [BD + Thalid] vs. BD; p < 0.05). Also thalidomide prevented kidney function failure by reduced urea (148.3 ± 4.4 mg/dL [BD + Thalid] vs. BD; p < 0.05), and creatinine (1.1 ± 0.14 mg/dL [BD + Thalid] vs. BD; p < 0.05).
Conclusions: The immunomodulatory properties of thalidomide were effective in decreasing systemic and local immunologic response, leading to diminished renal damage, as reflected in the decrease of urea and creatinine levels. These results suggest that use of thalidomide may represent a potential strategy for treating in BD kidney organ donors.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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