DECREASED IL-4 PRODUCTION IN NEW-ONSET TYPE-I INSULIN-DEPENDENT DIABETES-MELLITUS

IL-4 has been shown to prefect against diabetes development in rodent models of insulin-dependent (type I) diabetes mellitus (IDDM). To stud y IL-4 production in human IDDM, PBMC from IDDM patients and controls were stimulated in vitro with PHA, anti-CD3 mAb, or PMA and ionophore, IL-4 production by PBMC or T cells was strongly impaired in IDDM pati ents at diabetes onset (p < 0.0001), The mean IL-4 response of patient s in the honeymoon stage was higher than the mean of the new onset pat ients, but significantly lower than the control group (p = 0.01), Pati ents with IDDM of longer duration (> 2 yr) showed a wide range of IL-4 responses and their mean IL-4 response was lower than the controls; h owever, the difference was not statistically significant, IL-4 mRNA le vels were measured using competitive reverse transcription PCR, The re sults showed greatly reduced mRNA levels in new onset IDDM, In contras t, IL-1 production (measured by ELISA) and IFN-gamma mRNA (measured by reverse transcription PCR) were not significantly different in IDDM, The results suggest an imbalance of inflammatory vs anti-inflammatory cytokine production at the onset of IDDM, Deficient IL-4 production as seen at the onset of IDDM may play a role in the development of diabe tes by allowing the inflammatory/autoimmune process in pancreatic isle ts to progress.