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Chemiluminescence and Superoxide Anion Production by Leukocytes from Diabetic Patients^*

SUDHIR V. SHAH, J. D. WALLIN and STEVEN D. EILENJ

Department of Medicine, Veterans Administration Medical Center; and Tulane University School of Medicine New Orleans, Louisiana 70112

Address correspondence and requests for reprints to: Sudhir V. Shah, Department of Medicine, Tulane Medical School, 1430 Tulane Avenue, New Orleans, Louisiana 70112.

Stimulated neutrophils exhibit a burst of oxidative metabolism which results in the formation of superoxide anion and other oxygen species that participate in bacterial killing. Chemiluminescence is also produced and is a sensitive measure of oxidative metabolism and correlates well with antimicrobial activity. Since infection is an important cause of morbidity and mortality in diabetic patients we examined chemiluminescence and superoxide production byleukocytes from diabetics in the resting state and in response to a soluble (phorbol myristate acetate) and to a particulate stimulus (opsonized zymosan). No significant difference in the resting chemiluminescence was observed. However, the resting superoxide anion production by patients’ leukocytes was significantly higher in autologous serum; when patients’ leukocytes were placed in normal serum, a significant reduction in the resting superoxide anion production was observed. Using phorbol myristate acetate as a stimulus, leukocytes from diabetic patients had a markedly reduced chemiluminescence response [controls 388 ± 48, n = 22, patient 220 ± 37, peak cpm x 10³/10⁶P leukocytes, n = 22, (P < 0.01)] and reduced superoxide anion response [controls 30.1 ±3.8, n = 16, patients 13.3 ± 2.6 nmol/15 min /10⁶ P leukocytes, n = 16 (P < 0.001)]. Significantly reduced chemiluminescence response (P < 0.05) and superoxide production (P < 0.05) by leukocytes from diabetic patients were also observed using opsonized zymosan as a stimulus. No significant effects onchemiluminescence or superoxide response to phorbol myristate acetate were observed with cross-incubation studies in which patients’ leukocytes were placed in normal serum or control leukocytes in patient serum. In vitro addition of insulin (25 µU; 100 µU/ml) had no significant effect on patient cell response; similarly increasing the glucose concentration from 100 mg/dl to 200 mg/dl and 400 mg/dl had no significant effect on control cell response. Glucagon in a lower concentration (200 pg/ml) had no significant effect; only at a higher concentration (400 pg/ml), it caused an inhibition of the phorbol stimulated chemiluminescence and superoxide response of control leukocytes. These results show an impaired oxidative burst by leukocytesfrom diabetic patients which may contribute to impaired bacterial killing and may explain, in part, the morbidity and mortality in diabetic patients suffering from infection..

^* This research was supported in part by the Medical Research Service of the Veterans Administration Hospital, New Orleans, Louisiana.

Recipient of New Investigator Research Award IR23AM2845-01 from the NIADDK.

Research Fellowship supported by the William Howard and John S. Gillentine Memorial Scholarship Fund.

Received January 13, 1983.

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