The GH/IGF1 axis may modulate inflammatory processes. However, the relationship seems complicated as both pro- and anti-inflammatory effects have been demonstrated.
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 α (TNFα (TNFA)), interleukin 6 (IL6), and IL1β (IL1B) and the acute phase proteins (APPs) C-reactive protein (CRP), haptoglobin, orosomucoid, YKL40 (CHI3L1), and fibrinogen were measured.
During GH treatment, IGF1 (median 131 (Inter-quartile range (IQR) 112–166) vs 390 (322–524) μg/l, P=0.002) increased together with TNFα (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) μM, P=0.002). By contrast, orosomucoid decreased (18.0 (15.5–24.3) vs 15.0 (15.0–17.0) μM, 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) μM, 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.
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.