Altered association of interleukin-6 with sex steroids in lipid metabolism disorder in men with prostate cancer receiving androgen deprivation therapy

Prostate. 2012 Aug 1;72(11):1207-13. doi: 10.1002/pros.22471. Epub 2011 Dec 27.

Abstract

Background: Interleukin-6 produced in adipose tissue plays a role in lipid metabolism, and also interacts with sex steroids. This study was performed to elucidate the mechanism of lipid metabolism disorder during androgen deprivation therapy (ADT) in terms of the association of interleukin-6 with sex steroids.

Methods: Seventy-two patients with localized prostate cancer were prospectively studied based on their body-composition and blood samples before and after ADT for 6 months.

Results: Before ADT, serum interleukin-6 levels were inversely correlated with serum total-testosterone (rs = -0.305, P = 0.009) and dihydrotestosterone (rs = -0.380, P = 0.006) concentrations, but not correlated with adrenal androgen or estradiol levels. Pretreatment interleukin-6 levels were positively correlated with %body fat (rs = 0.349, P = 0.003) and %visceral fat (rs = 0.384, P = 0.001). After ADT, %body fat increased (P < 0.001) and lean body mass decreased (P = 0.036). After ADT, in contrast to the pretreatment relationship, interleukin-6 levels were positively correlated with total-testosterone concentrations (rs = 0.343, P = 0.003), and were positively correlated also with levels of androstenedione (rs = 0.351, P = 0.002) and estoradiol (rs = 0.335, P = 0.004). Interleukin-6 levels were equivalent between before and after ADT (2.02 vs. 2.16 pg/ml, P = 0.205), but the positive correlation between interleukin-6 levels and %body or %visceral fat noted before ADT disappeared after ADT.

Conclusions: Posttreatment interleukin-6 levels had a strong positive correlation with total-testosterone, androstenedione, and estradiol levels, suggesting that a regulation loop may emerge between these sex steroids and interleukin-6 during ADT. The altered association between interleukin-6 and sex steroids is possibly involved in ADT-related lipid metabolism disorder with unchanged interleukin-6 levels despite increased %body fat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Androgen Antagonists / therapeutic use*
  • Body Composition
  • Gonadal Steroid Hormones / blood
  • Gonadal Steroid Hormones / metabolism*
  • Humans
  • Interleukin-6 / metabolism*
  • Lipid Metabolism Disorders / blood
  • Lipid Metabolism Disorders / metabolism*
  • Male
  • Middle Aged
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Androgen Antagonists
  • Gonadal Steroid Hormones
  • Interleukin-6
  • Tumor Necrosis Factor-alpha