GH strongly affects serum concentrations of mannan-binding lectin: Evidence for a new IGF-I independent immunomodulatory effect of GH

Studies in animals and humans indicate that GH and IGF-I modulate immune fu nction. Recently, it was reported that GH therapy increased the mortality i n critically ill patients. The excessive mortality was almost entirely attr ibutable to septic shock or multiorgan failure, suggesting that a GH-induce d modulation of immune function was involved. In the present study, we exam ined whether GH or IGF-I influences the serum concentrations of mannan-bind ing lectin (MBL). MBL is a plasma protein of the innate immune system that initiates the complement cascade and activates inflammation after binding t o 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 o f MBL were more than doubled during GH treatment, whereas no changes were o bserved 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. Subseque ntly, we studied 30 healthy persons and 25 GH-deficient (GHD) patients rand omized to treatment with GH or placebo in a double-blinded manner, and furt her included samples from 23 patients with active acromegaly examined befor e and after treatment with octreotide or the GH-receptor antagonist pegviso mant for 3 months. Baseline concentrations of MBL were lower in GHD patient s and higher in acromegalic patients than in healthy subjects (P < 0.02). T reatment with GH doubled the MBL concentrations in healthy subjects and alm ost quadrupled the concentrations in GHD patients; whereas in acromegalic p atients, 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, significantl y increases MBL concentrations. The clinical consequences of this new link between the endocrine and the immune system remain to be elucidated.