Altered association of interleukin-6 with sex steroids in lipid metabolism disorder in men with prostate cancer receiving androgen deprivation therapy.
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.
Division of Urology, Department of Regenerative and Transplant Medicine, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
Shuichi
S
Komatsu
Noboru
N
Hara
Fumio
F
Ishizaki
Tsutomu
T
Nishiyama
Itsuhiro
I
Takizawa
Etsuko
E
Isahaya
Takashi
T
Kawasaki
Kota
K
Takahashi
D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D001823:Body Composition; D012739:Gonadal Steroid Hormones / Q000097:blood / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D052439:Lipid Metabolism Disorders / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000726:Androgen Antagonists; D012739:Gonadal Steroid Hormones; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha