GH activity and markers of inflammation: a crossover study in healthy volunteers treated with GH and a GH receptor antagonist

Introduction: The GH/IGF1 axis may modulate inflammatory processes. However, the relationship seems complicated as both pro-and anti-inflammatory effects have been demonstrated. Methods/design: Twelve healthy volunteers (mean age 36, range 27-49 years) were treated in random order with increasing doses of GH for 3 weeks (first week 0.01 mg/kg per day, second week 0.02 mg/kg per day, and third week 0.03 mg/kg per day) or a GH receptor antagonist (pegvisomant; first week 10 mg/day and last two weeks 15 mg/day), separated by 8 weeks of washout. Circulating levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF alpha (TNFA)), interleukin 6 (IL6), and IL1 beta (IL1B) and the acute phase proteins (APPs) C-reactive protein (CRP), haptoglobin, orosomucoid, YKL40 (CHI3L1), and fibrinogen were measured. Results: During GH treatment, IGF1 (median 131 (Inter-quartile range (IQR) 112-166) vs 390 (322-524) mu g/l, P=0.002) increased together with TNF alpha (0.87 (0.74-1.48) vs 1.27 (0.80-1.69) ng/l, P=0.003), IL6 (1.00 (0.83-1.55) vs 1.35 (0.80-4.28) ng/l, P=0.045), and fibrinogen (9.2 (8.8-9.6) vs 11.1 (9.4-12.4) mu M, P=0.002). By contrast, orosomucoid decreased (18.0 (15.5-24.3) vs 15.0 (15.0-17.0) mu M, P=0.018). CRP, YKL40, and haptoglobin were unchanged. During pegvisomant treatment, IGF1 decreased (139 (117-171) vs 91 (78-114) ng/ml, P=0.005). Orosomucoid (21.0 (16.3-23.8) vs 22.0 (17.0-29.3) mu M, P=0.036) and CRP (1.00 (0.62-1.77) vs 1.43 (0.71-3.29) mg/l, P=0.074) increased without an increase in pro-inflammatory cytokines. Conclusions: GH/IGF1 action appears to modulate the initial stage of the inflammatory response as well as downstream processes elucidated by levels of APPs. The data suggest a complicated relationship not allowing any simple conclusions as to whether GH/IGF1 actions have mainly pro-or anti-inflammatory effects in vivo.