INSULIN-LIKE GROWTH-FACTOR-I IS AN INDEPENDENT COREGULATORY MODULATOROF NATURAL-KILLER (NK) CELL-ACTIVITY

We aimed to investigate the natural killer (NK) cell activity in hGH-d eficient adults and to analyze the effect of insulin-like growth facto r (IGF)-I in vivo and in vitro on NK cell activity. NK cell activity w as measured in a 4-h nonisotopic assay with europium-labeled and cryop reserved K-562 cells. NK-cell numbers were measured after incubation w ith murine monoclonal CD3 and CD16 antibodies by flow cytometry analys is. In a cross-sectional study, the basal and interferon-beta (IFN-bet a) stimulated (1000 IU/ml) NK cell activity of 15 hGH-deficient patien ts and 15 age- and sex-matched controls was measured. The percentages and absolute numbers of CD3(-)/16(+) NK-cells were not significantly d ifferent in the patient vs. control group. The basal and IFN-beta stim ulated NK cell activity however was significantly decreased in the pat ient vs. control group at all effector/target (E/T) cell ratios from 1 2.5-100 (e.g. 17 +/- 3 vs. 28 +/- 3% lysis without IFN-beta, P < 0.05, and 42 +/- 4 vs. 57 +/- 4% lysis with IFN-beta, P < 0.05; both at E/T 50). IGF-I levels of patients and controls showed a significant posit ive correlation with NK cell activity (r = 0.37; P < 0.05). In an IGF- I in vitro study (IGF-I in vitro 250-1250 mu g/L), the basal and IFN-b eta stimulated NI( cell activity of 13 hGH-deficient patients and of 1 8 normal subjects was significantly enhanced by IGF-I in vitro (e.g. G H-deficient patients: 9 +/- 2 vs. 10 +/- 2% lysis without IFN-beta, P < 0.05 and 25 +/- 4 vs. 30 +/- 4% lysis with IFN-beta, P < 0.005; and normal subjects: 15 +/- 3 vs. 23 +/- 3% lysis without IFN-beta, P < 0. 001 and 35 +/- 4 vs. 44 +/- 5% lysis with IFN-beta, P < 0.001; both at IGF-I 500 mu g/L). In summary, in our cross-sectional study, adult GH -deficient patients showed a significantly lower basal and IFN-beta st imulated NK cell activity than matched controls, despite equal NK cell numbers. IGF-I levels of patients and controls showed a weak positive correlation with NK cell activity. In an in vitro study, IGF-I signif icantly enhanced basal and IFN-beta stimulated NK cell activity of hGH -deficient patients and also of normal subjects. The decreased NK cell activity in GH-deficient patients may be caused at least in part by l ow serum IGF-I levels. IGF-I appears to be an independent coregulatory modulator of NK cell activity.