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GH Strongly Affects Serum Concentrations of Mannan-Binding Lectin: Evidence for a New IGF-I Independent Immunomodulatory Effect of GH

Medical Department M (Endocrinology and Diabetes) (T.K.H., R.D., A.F., J.O.L.J., J.S.C.), Aarhus University Hospital, DK-8000 Aarhus C; Department of Medical Microbiology and Immunology (S.T.), University of Aarhus, DK-8000 Aarhus C; Department of Internal Medicine and Endocrinology (A.M.R.), Hvidovre University Hospital, DK-2650 Hvidovre, Denmark; and Department of Endocrinology (P.T.), Christie Hospital, Manchester, United Kingdom M20 4BX

Address all correspondence and requests for reprints to: Troels Krarup Hansen, M.D., Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, Norrebrogade 42-44, DK-8000 Aarhus C, Denmark. E-mail: tkh{at}dadlnet.dk

Abstract

Studies in animals and humans indicate that GH and IGF-I modulate immune function. Recently, it was reported that GH therapy increased the mortality in critically ill patients. The excessive mortality was almost entirely attributable to septic shock or multiorgan failure, suggesting that a GH-induced modulation of immune function was involved. In the present study, we examined whether GH or IGF-I influences the serum concentrations of mannan-binding lectin (MBL). MBL is a plasma protein of the innate immune system that initiates the complement cascade and activates inflammation after binding to carbohydrate structures on microbial surfaces.

We performed a cross-over study of 16 healthy men examined during a control period, and during treatment with either GH or IGF-I for 6 d. The levels of MBL were more than doubled during GH treatment, whereas no changes were observed in the IGF-I group or during the control period (P < 0.001). IGF-I levels were elevated similarly during treatment with GH and IGF-I. Subsequently, we studied 30 healthy persons and 25 GH-deficient (GHD) patients randomized to treatment with GH or placebo in a double-blinded manner, and further included samples from 23 patients with active acromegaly examined before and after treatment with octreotide or the GH-receptor antagonist pegvisomant for 3 months. Baseline concentrations of MBL were lower in GHD patients and higher in acromegalic patients than in healthy subjects (P < 0.02). Treatment with GH doubled the MBL concentrations in healthy subjects and almost quadrupled the concentrations in GHD patients; whereas in acromegalic patients, the levels of MBL were reduced to approximately two thirds of the initial values during treatment with octreotide or pegvisomant.

Our results demonstrate that treatment with GH, but not IGF-I, significantly increases MBL concentrations. The clinical consequences of this new link between the endocrine and the immune system remain to be elucidated.

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