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Interleukin-6 May Not Affect Bone Resorption Marker CTX or Bone Formation Marker P1NP in Humans
Louise L Lehrskov1, Sasha Kjeldsen2,3, Mark P Lyngbæk1
1The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Context:
Interleukin 6 (IL-6) contributes to bone remodeling in preclinical studies. Clinical trials investigating the role of IL-6 in bone remodeling are limited.
Objective:
To investigate if IL-6 regulates bone remodeling in humans.
Design:
Plasma concentrations of the bone resorption marker carboxy-terminal type I collagen crosslinks (CTX) and of the bone formation marker procollagen type 1 N-terminal propeptide (P1NP) were measured during a mixed-meal tolerance test (MMTT) in 3 placebo-controlled human studies.
Participants:
Five healthy individuals participated in study 1; 52 obese individuals, in study 2; and 10 healthy individuals, in study 3.
Interventions:
Study 1 was a single-blinded crossover study consisting of a 1-h infusion of saline (placebo) or the IL-6 receptor antibody tocilizumab followed by an exercise bout. Study 2 was a randomized, double-blinded 12-week exercise training intervention study. Participants received infusions of saline or tocilizumab. Study 3 was a randomized, double-blinded, crossover study consisting of 30 min infusion of saline or IL-6.
Main Outcomes Measures:
Effect of IL-6 on CTX levels.
Results:
CTX was significantly (P < 0.01) decreased during MMTTs in all 3 studies. Treatment with tocilizumab did not affect exercise or meal induced changes in plasma CTX or P1NP concentrations acutely (study 1) or after a 12-week treatment period (study 2). Exogenous IL-6 had no effect on CTX or P1NP plasma concentrations (study 3).
Conclusions:
IL-6 may not regulate bone remodeling in humans.
