Low-dose testosterone protects against renal ischemia-reperfusion injury by increasing renal IL-10-to-TNF-α ratio and attenuating T-cell infiltration

Chetan N. Patil, Kedra Wallace, Babbette D. La Marca, Mohadetheh Moulana, Arnaldo Lopez-Ruiz, Andrea Soljancic, Luis A. Juncos, Joseph P. Grande, Jane F. Reckelhoff

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Renal ischemia-reperfusion (I/R) in male rats causes reductions in plasma testosterone, and infusion of testosterone 3 h postreperfusion is protective. We tested the hypotheses that acute high doses of testosterone promote renal injury after I/R, and that acute low-dose testosterone is protective by the following: 1) increasing renal IL-10 and reducing TNF-α; 2) its effects on nitric oxide; and 3) reducing intrarenal T-cell infiltration. Rats were subjected to renal I/R, followed by intravenous infusion of vehicle or testosterone (20, 50, or 100 μg/kg) 3 h postreperfusion. Low-dose testosterone (20 μg/kg) reduced plasma creatinine, increased nitrate/nitrite excretion, increased intrarenal IL-10, and reduced intrarenal TNF-α, whereas 50 μg/kg testosterone failed to reduce plasma creatinine, increased IL-10, but failed to reduce TNF-α. A higher dose of testosterone (100 mg/kg) not only failed to reduce plasma creatinine, but significantly increased both IL-10 and TNF-α compared with other groups. Lowdose nitro-L-arginine methyl ester (1 mg·kg-1·day-1), given 2 days before I/R, prevented low-dose testosterone (20 μg/kg) from protecting against I/R injury, and was associated with lack of increase in intrarenal IL-10. Intrarenal CD4+ and CD8+ T cells were significantly increased with I/R, but were attenuated with low-dose testosterone, as were effector T helper 17 cells. The present studies suggest that acute, low-dose testosterone is protective against I/R AKI in males due to its effects on inflammation by reducing renal T-cell infiltration and by shifting the balance to favor anti-inflammatory cytokine production rather than proinflammatory cytokines.

Original languageEnglish (US)
Pages (from-to)F395-F403
JournalAmerican Journal of Physiology - Renal Physiology
Volume311
Issue number2
DOIs
StatePublished - Aug 1 2016

Keywords

  • Acute kidney injury
  • Androgens
  • Effector T cells
  • Inflammation
  • Males
  • Th17

ASJC Scopus subject areas

  • Physiology
  • Urology

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