Acquired Defect in Interleukin-2 Production in Patients with Type I Diabetes Mellitus

Abstract

Deficient production of interleukin-2 has been reported in Type I diabetes, but its cause has not been elucidated. We therefore measured interleukin-2 production in 27 patients with Type I diabetes, 20 patients with Type II diabetes (6 requiring insulin), 5 monozygotic twin pairs discordant for Type I diabetes, and 10 nondiabetic persons with islet-cell antibodies. Interleukin-2 production was decreased in patients with Type I diabetes as compared with controls (35.8 +/- 2.5 vs. 61.6 +/- 4.6 percent, P less than 0.001). Interleukin-2 production did not differ between patients with Type II diabetes and controls, regardless of whether the patients used insulin. Twins with Type I diabetes had decreased interleukin-2 production as compared with normal controls (33.2 +/- 5.4 vs. 61.6 +/- 4.6 percent, P less than 0.001) and with their nondiabetic twins (33.2 +/- 5.4 vs. 54.5 +/- 3.4 percent, P less than 0.005). Interleukin-2 production in nondiabetic twins and in nondiabetic persons with islet-cell antibodies was normal. There was no correlation between glycosylated hemoglobin levels and interleukin-2 production in any diabetic group. We conclude that patients with Type I diabetes have an acquired defect in interleukin-2 production, whereas patients with Type II diabetes do not, and that this defect is not correlated with an ongoing autoimmune process, with hyperglycemia, or with insulin administration or oral hypoglycemic therapy. Thus, the defect appears to be related to marked beta-cell destruction, although not to the metabolic consequences thereof or the responsible autoimmune process.

Decreased in vitro production of interferon-gamma and interleukin-2 in whole blood of patients with schizophrenia during treatment

“…2 The fact that this feature was observed only in the acutely ill, but not in the residual patients 15,30 is also worthy of note. Furthermore, as with type-I diabetes, where low IL-2 production is obviously acquired, and not inherited, 36 we found decreased IFN-␥ production in the acutely schizophrenic, but not in unaffected first degree relatives within families showing multiple occurrence of schizophrenia. 30 This finding also suggests that the deficit is associated with the active disease, rather than with a genetic predisposition.…”

“…35 This was also present only in affected children from monozygotic twin pairs who were discordant for the disease. 36 In rheumatoid arthritis, a lowered IL-2 production can be seen, 37 especially in the active disease when the joints become eroded. 38 Increased levels of sIL-2R have also repeatedly been reported 39 which were correlated with the rheumatic disease activity.…”

Multiple immuno-regulatory defects in type-1 diabetes

“…Others have suggested a global T cell defect in the disease, too (61). Low T cell IL-2 production was reported in IMD patients that appeared to be related to marked β cell destruction (62). Another study found IL-2 and soluble IL-2 receptor secretion defects in both newly diagnosed and longstanding diabetic patients (63).…”

Oral insulin for diabetes prevention in NOD mice: potentiation by enhancing Th2 cytokine expression in the gut through bacterial adjuvant

“…Indeed, Zhang et al [28] recently showed proliferation of Th2 effector cells and prevention of apoptotic cell death in the presence of IL-2 while prolonged, dramatic expansion of Th1 cells occurred during IL-2 deficiency. Impaired IL-2 production has been reported to be a characteristic of IDDM and its animal models [29][30][31][32]. A protective effect of IL-2 injections was reported in a BB rat line with high diabetes risk [33] and transgenic mice expressing IL-2 under the rat insulin promotor developed apparently benign insulitis because progression to diabetes was rarely observed [34].…”