Endocrine Abstracts (2011) 26 P242

Relationship between GH activity and markers of inflammation: a cross-over study of healthy volunteers treated with GH and a GH antagonist for 3 weeks

M Andreassen1, J Frystyk2, J Faber1 & L Ø Kristensen1

1Herlev Hospital Department of Internal Medicine O, University of Copenhagen, Copenhagen, Denmark; 2Medical Research Laboratories, Clinical Institute and Medical Department M, Aarhus University Hospital, Aarhus, Denmark.

Introduction: Observations in patients with GH disturbances and in normal populations have suggested that GH/IGF1 activity could have anti-inflammatory effects. On the other hand, in vitro studies have shown that IGF1 may stimulate the immune system.

Methods/design: The study population consisted of 12 healthy volunteers (mean age 36, range 27–49 years) treated with GH for 3 weeks (1st week 0.01 mg/day, 2nd 0.02 mg/day, 3rd 0.03 mg/day) and subsequently with a GH antagonist (pegvisomant) (1st week 10 mg/day, last 2 weeks 15 mg/day) or visa versa. Wash-out 8 weeks. Circulating levels of tumour necrosis factor-α (TNF-α), interleukin 6 (IL6), CRP, YKL-40, haptoglobin, orosomucoid and fibrinogen were measured after stimulation and inhibition of GH action.

Results: GH treatment compared to pegvisomant treatment led to an increase in serum IGF1 (median 393 (IQR 346–543) vs 91 (78–114) ng/ml, P=0.005) and in TNF-α (1.44 (0.97–1.75) vs 1.08 (0.74–1.48) pg/ml, P=0.047), haptoglobin 10.0 (8.0–18.5) vs 9.0 (6.8–13.8) μM, P=0.051) and fibrinogen (10.8 (9.2–12.2) vs 8.5 (7.4–10.6) μM, P=0.005). By contrast orosomucoid (16.0 (15.0–19.5) vs 22.0 (17.0–29.3) μM, P=0.005) and CRP (0.64 (0.55–1.71) vs 1.43 (0.71–3.29) mg/l, P=0.037) were reduced during GH treatment. IL6 and YKL-40 were unchanged. Compared to baseline there was an increase in serum GH after treatment with both GH (0.26 (0.13–0.51) vs 4.33 (1.81–7.25) ng/ml, P=0.005) and pegvisomant (0.26 (0.13–0.51) vs 1.02 (0.34–3.48) ng/ml, P=0.013). Serum pegvisomant was 8714 (3881–15666) ng/ml.

Conclusions: The data support that high GH/IGF1 activity stimulates the initial phase of the innate immune response evaluated by the pro-inflammatory cytokine TNF-α. However the opposing results on down stream acute phase proteins (fibrinogen and haptoglobin versus orosomucoid and CRP) support a complex interplay between GH/IGF1 action and the inflammatory cascade that does not allow simple conclusions on whether GH/IGF1 action has pro- or anti-inflammatory effects in vivo.

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