Use este identificador para citar ou linkar para este item: http://www.repositorio.ufc.br/handle/riufc/16952
Título: Target inhibition of IL-1 receptor prevents ifosfamide induced hemorrhagic cystitis in mice
Autor(es): Leite, Caio A. V. G.
Alencar, Viviane T. L.
Melo, Davi L. R.
Melo, Paulo H.
Mourão, Lívia T. C.
Wong, Deysi V. T.
Magalhães, Pedro J. C.
Santos, Armênio A.
Brito, Gerly A. C.
Lima-Júnior, Roberto C. P.
Cunha, Fernando Q.
Ribeiro, Ronaldo A.
Mota, José M. S. C.
Palavras-chave: Bexiga Urinária
Cistite
Interleucina-1
Anticorpos
Data do documento: Dez-2015
Editor: The Journal of Urology
Citação: LEITE, C. A. V. G. ; ALENCAR, V. T. L. ; MELO, D. L. R. ; MOTA, J. M. S. C. ; MELO, P. H. ; MOURÃO, L. T.C. ; WONG, D. V. T. ; MAGALHÃES, P. J. C. ; SANTOS, A. A. ; BRITO, G. A.C. ; LIMA-JÚNIOR, R. C. P. ; CUNHA, F. Q. ; RIBEIRO, R. A. (2015)
Abstract: Purpose Hemorrhagic cystitis is an important dose limiting side effect of ifosfamide based cancer chemotherapy. Despite chemoprophylaxis inflammation can still be found in cystoscopy guided biopsies. Previous studies confirmed the role of TNF-α and IL-1β. We evaluated the protective effect of the IL-1R antagonist anakinra and the anti-TNF-α antibody infliximab in experimental ifosfamide induced hemorrhagic cystitis. Materials and Methods Hemorrhagic cystitis was induced by an injection of ifosfamide (400 mg/kg intraperitoneally) in Swiss wild-type C57Bl/6, IL-1R–/–, TNFR1–/– or TNFR1/R2–/– mice. Mice were treated 30 minutes before ifosfamide with anakinra (100 mg/kg intraperitoneally), infliximab (5 mg/kg intraperitoneally) or vehicle. Visceral nociception was evaluated after hemorrhagic cystitis induction. At 12 hours the animals were sacrificed. Bladders were harvested to assess bladder wet weight, vascular permeability, macroscopic and microscopic findings, muscle contractility, and for cystometrography. Inflammatory cell infiltration was assessed by myeloperoxidase assay and flow cytometry. Results Anakinra attenuated hemorrhage, edema, neutrophil infiltration, visceral hyperalgesia and bladder dysfunction. IL-1R–/– mice also showed milder hemorrhagic cystitis. Infliximab inhibited bladder edema and visceral hyperalgesia without preventing hemorrhage, bladder dysfunction, neutrophils or accumulation. Additionally, the lack of TNFR1 decreased bladder edema but not cell infiltration whereas concomitant deficiency of TNFR1 and TNFR2 resulted in worse hemorrhagic cystitis. Conclusions Anakinra is effective for preventing experimentally ifosfamide induced hemorrhagic cystitis. It seems that neutrophil and macrophage infiltration in this circumstance depends on IL-1 signaling through IL1R. Possibly TNFR2 has a protective role in hemorrhagic cystitis.
Descrição: LEITE, Caio A. V. G. ; ALENCAR, Viviane T. L. ; MELO, Davi L. R. ; MOTA, José M. S. C. ; MELO, Paulo H. ; MOURÃO, Lívia T. C. ; WONG, Deysi V. T. ; MAGALHÃES, Pedro J. C. ; SANTOS, Armênio A. ; BRITO, Gerly A.C. ; LIMA-JÚNIOR, Roberto C. P. ; CUNHA, Fernando Q. ; RIBEIRO, Ronaldo A. Target Inhibition of IL-1 receptor prevents ifosfamide induced hemorrhagic cystitis in mice. The Journal of Urology , Baltimore, v. 194, n. 6, p. 1777-86, dec. 2015,
URI: http://www.repositorio.ufc.br/handle/riufc/16952
ISSN: 0022-5347
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