title: Proinflammatory Cytokine Infusion Attenuates LH's Feedforward on Testosterone Secretion: Modulation by Age.
abstract: BACKGROUND
  In the experimental animal, inflammatory signals quench LH's feedforward drive of testosterone (T) secretion and appear to impair GnRH-LH output. The degree to which such suppressive effects operate in the human is not known.
  
  
  OBJECTIVE
  To test the hypothesis that IL-2 impairs LH's feedforward drive on T and T's feedback inhibition of LH secretion in healthy men.
  
  
  METHODS
  Mayo Center for Translational Science Activities.
  
  
  METHODS
  A total of 35 healthy men, 17 young and 18 older.
  
  
  METHODS
  Randomized prospective double-blind saline-controlled study of IL-2 infusion in 2 doses with concurrent 10-minute blood sampling for 24 hours.
  
  
  METHODS
  Deconvolution analysis of LH and T secretion.
  
  
  RESULTS
  After saline injection, older compared with young men exhibited reduced LH feedforward drive on T secretion (P < .001), and decreased T feedback inhibition of LH secretion (P < .01). After IL-2 injection, LH's feedforward onto T secretion declined markedly especially in young subjects (P < .001). Concomitantly, IL-2 potentiated T's proportional feedback on LH secretion especially in older volunteers.
  
  
  CONCLUSIONS
  This investigation confirms combined feedforward and feedback deficits in older relative to young men given saline and demonstrates 1) joint mechanisms by which IL-2 enforces biochemical hypogonadism, viz, combined feedforward block and feedback amplification; and 2) unequal absolute inhibition of T and LH secretion by IL-2 in young and older men. These outcomes establish that the male gonadal axis is susceptible to dual-site suppression by a prototypic inflammatory mediator. Thus, we postulate that selected ILs might also enforce male hypogonadism in chronic systemic inflammation.
authors.affiliation: Endocrine Research Unit (J.V., R.Y.), Mayo Clinic College of Medicine, Center for Translational Science Activities, and Primary Care Internal Medicine (P.T.), Mayo Clinic, Rochester, Minnesota 55905; and Leiden University Medical Center (F.R.), 2333ZA Leiden, The Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: Veldhuis
authors.affiliation: Endocrine Research Unit (J.V., R.Y.), Mayo Clinic College of Medicine, Center for Translational Science Activities, and Primary Care Internal Medicine (P.T.), Mayo Clinic, Rochester, Minnesota 55905; and Leiden University Medical Center (F.R.), 2333ZA Leiden, The Netherlands.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Yang
authors.affiliation: Endocrine Research Unit (J.V., R.Y.), Mayo Clinic College of Medicine, Center for Translational Science Activities, and Primary Care Internal Medicine (P.T.), Mayo Clinic, Rochester, Minnesota 55905; and Leiden University Medical Center (F.R.), 2333ZA Leiden, The Netherlands.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Roelfsema
authors.affiliation: Endocrine Research Unit (J.V., R.Y.), Mayo Clinic College of Medicine, Center for Translational Science Activities, and Primary Care Internal Medicine (P.T.), Mayo Clinic, Rochester, Minnesota 55905; and Leiden University Medical Center (F.R.), 2333ZA Leiden, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Takahashi
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology*; D018592:Cross-Over Studies; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D025461:Feedback, Physiological / Q000187:drug effects*; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D013739:Testosterone / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016207:Cytokines; C508594:IL2 protein, human; D007376:Interleukin-2; D013739:Testosterone; D007986:Luteinizing Hormone