IMMUNOLOGICAL EFFECTS OF A HYPERINSULINEMIC EUGLYCEMIC INSULIN CLAMP IN HEALTHY-MALES

The purpose of this study was to determine the in-vivo and in-vitro ef fects of insulin, at physiological and supraphysiological concentratio ns, on the human immune system. Ten healthy young men went through a s equential two-step hyperinsulinaemic euglycaemic clamp. Plasma insulin concentrations were increased from baseline (9.0 mu U/ml) to 49.1 mu U/ml after 1 h of insulin infusion (step I) and to 1281 mu U/ml (step II) after 2 h of infusion. As control experiments infusions of isotoni c saline were performed. The unstimulated natural killer (NK) cell act ivity among blood mononuclear cells (BMNC) increased in response to su praphysiological plasma insulin levels (baseline versus step II: 20.6 +/- 11.3 versus 27.8 +/- 14.4%). The percentages of the CD16(+) NK cel ls did not change, indicating an enhanced cytotoxic capability per ind ividual NK cell. Insulin also slightly increased the activity of NK ce lls in vitro. A decline at step II in the concentrations of monocytes (0.29 +/- 0.09 versus 0.12 +/- 0.03 x 10(9)/L), lymphocytes (1.57 +/- 0.46 versus 1.22 +/- 0.25 x10(9)/L), and CD16(+)(24.2 +/- 17.5 versus 16.7 +/- 11.2 x 10(7)/L). CD14(+)(20.9 +/- 10.8 versus 8.6 +/- 3.9 x 1 0(7)/L), HLA-DR+ (37.2 +/- 22.1 versus 19.2 +/- 10.7 x 10(7)/L) and CD 45RO(+)(91.6 +/- 33.4 versus 61.7 +/- 6.4 x 10(7)/L) cells as well as in the percentages of CD14(+) cells (11.2 +/- 4.7 versus 6.4 +/- 2.3%) and CD14(+)/HLA-DR+ monocytes (9.7 +/- 3.9 versus 4.8 +/- 2.8%) were observed. No changes were found at step I. Hyperinsulinaemia did not c hange the percentages of the CD3(+), CD3(+), CD8(+), CD19(+), CD56(+), CD11a(+), CD45RO(+) and CD45RA(+) cells, the numbers of circulating i mmunoglobulin (Ig)G-, IgA- and IgM-secreting cells, or the proliferati ve responses of BMNC to phytohaemagglutinin, purified derivative of tu berculin or interleukin (IL)-2. Hyperinsulinaemia did not change the i n-vitro sensibility to insulin. In conclusion, supraphysiological insu lin levels increased the activity of the individual NK cells, but decr eased the numbers of NK cells, lymphocytes and activated monocytes. Th e findings are presumably of minor clinical relevance but may indicate an insulin-induced immune activation.