Insulin-like growth factor I is an independent coregulatory modulator of natural killer (NK) cell activity.

We aimed to investigate the natural killer (NK) cell activity in
hGH-deficient adults and to analyze the effect of insulin-like
growth factor (IGF)-I in uivo and in vitro on NK cell activity. NK
cell activity was measured in a 4-h nonisotopic assay with
europium-labeled and cryopreserved K-562 cells. NK-cell numbers
were measured after incubation with murine monoclonal CD3 and CD16
antibodies by flow cytometry analysis. In a cross-sectional study,
the basal and interferon- p (IFN-P) stimulated (1000 IU/ml) NK cell
activity of 15 hGHdeficient patients and 15 age- and sex-matched
controls was measured. The percentages and absolute numbers of
CD3./16+ NK-cells were not significantly different in the patient
vs. control group. The basal and IFN-P stimulated NK cell activity
however was significantly decreased in the patient vs. control
group at all effecter/target (E/T) cell ratios from 12.5-100 (e.g.
17 ? 3 vs. 28 ? 3% lysis without IFN-P, P < 0.05, and 42 t 4 vs.
57 2 4% lysis with IFN-0, P < 0.05; both at E/T 50). IGF-I
levels of patients and controls showed a significant positive
correlation with NK cell activity (r = 0.37; P < 0.05). In an
IGF-I in vitro study (IGF-I in vitro 250-1250 kg/L), the basal and
IFN-P stimulated NK cell activity of 13 hGH-deficient patients and
of 18 normal subjects was significantly enhanced by IGF-I in vitro
(e.g. GH-deficient patients: 9 ? 2 us. 10 2 2% lysis without IFN-P,
P < 0.05 and 25 + 4 vs. 30 + 4% lysis with IFN-/3, P < 0.005;
and normal subjects: 15 + 3 vs. 23 ? 3% lysis without IFN-/3, P
< 0.001 and 35 2 4 us. 44 + 5% lysis with IFN-P, P < 0.001;
both at IGF-I 500 pg/L). In summary, in our cross-sectional study,
adult GH-deficient patients showed a significantly lower basal and
IFN-P stimulated 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 significantly enhanced basal and IFN-P stimulated NK
cell activity of hGH-deficient patients and also of normal
subjects. The decreased NK cell activity in GHdeficient patients
may be caused at least in part by low serum IGF-I levels. IGF-I
appears to be an independent coregulatory modulator of NK cell
activity. (Endocrinology 137: 5332-5336, 1996)