EVIDENCE OF EXVIVO AND INVITRO IMPAIRED NEUTROPHIL OXIDATIVE BURST AND PHAGOCYTIC CAPACITY IN TYPE-1 DIABETES-MELLITUS

In this study neutrophil (PMN) oxidative burst activity was investigat ed ex vivo and in vitro in comparison to the PMN-phagocytic functions ingestion and bacterial killing in poorly-controlled type 1 diabetic p atients. Luminol enhanced chemiluminescence in response to phorboleste rs as a measure of oxidative burst was assessed in a parallel detectin g microtiterplate luminometer in 40 poorly-controlled type 1 diabetic subjects. PMN ingestion was measured with [H-3]thymidine-labelled Stap hylococcus aureus in a kinetic radiometric assay. Microbicidal activit y was determined by pure plate counting of surviving bacteria (colony forming units, cfu) after defined pmn challenge. PMNs of type 1 diabet ic subjects showed a highly significant reduction of peak CL response in response to PMA compared to nondiabetic controls (P < 0.001) and PM N ingestion (51.8 +/- 4.6%) and bacterial killing (28.6 +/- 3.20%) wer e reduced as well (78.2 +/- 5.2% (IN) and 18.4 +/- 4.1% (BK), P < 0.01 , respectively). The in vitro data displayed impaired PMN oxidative bu rst activity at glucose concentrations greater-than-or-equal-to 13.8. mmol/l whereas PMN IN and BK were significantly reduced at glucose lev els greater-than-or-equal-to 27.75 mmol/l. In the control group there was a positive correlation of peak CL response and IN as well as BK (P < 0.05); in type 1 diabetic patients this was also true, but did not reach statistical significance. The data obtained in this study clearl y demonstrated impaired PMN oxidative burst activity and markedly redu ced ingestion and bacterial killing in type 1 diabetic patients ex viv o and in vitro. These findings suggest inhibitory effects of elevated glucose concentrations on various PMN-functions, which might be of cli nical importance concerning impaired host defense.