Anti-interleukin 2 receptor antibody attenuates low-dose streptozotocin-induced diabetes in mice

Abstract

Summary. Recent evidence indicates that activated T cells and macrophages play an important role in the induction of insulitis and diabetes in certain strains of mice treated with multiple subdiabetogenic doses of streptozotoein. In the present study, we treated C57BL/6J mice with five daily doses of 40 mg/ml streptozotocin and examined the prophylactic effect of an anti-interleukin 2 receptor monoclonal antibody (PC61). In mice treated with streptozotocin, interleukin 2 receptor-positive mononuclear cells were shown to infiltrate into the islets and soluble interleukin 2 receptors in the sera were significantly increased compared with control mice. The administration of PC61 to the mice attenuated the insulitis, and diminished interleukin 2 receptor-positive cells from islets and soluble interleukin 2 receptors in the sera. Moreover, the administration of PC61 significantly reduced the development of hyperglycaemia shown in these mice (12.8 _+ 1

Sodium Fusidate Ameliorates the Course of Diabetes Induced in Mice by Multiple Low Doses of Streptozotocin

“…Both of these findings suggest that there are important pathogenic differences between SZ-induced DM and the NOD mouse model of type 1 DM, since TNF-plays an age-dependent dichotomic role in the latter [15]. That anti-IL-2R mAb were incapable of counteracting the diabetogenic effects of SZ agrees with some but not all previously published findings [9,12]. Thus, Hatamori et al [12] showed a preventive effect of anti-IL-2R mAb prophylaxis in SZ-induced DM.…”

“…That anti-IL-2R mAb were incapable of counteracting the diabetogenic effects of SZ agrees with some but not all previously published findings [9,12]. Thus, Hatamori et al [12] showed a preventive effect of anti-IL-2R mAb prophylaxis in SZ-induced DM. Hence unlike in the NOD mouse [15] endogenous IL-2 is not required for the diabetogenic effects of SZ to occur in mice.…”

Streptozotocin-induced diabetes in mice lacking αβ T cells

“…In conclusion, the accumulated evidence suggests that MD-STZ induces severe pancreatic b cell injury which, at least on a NOD background, is further exacerbated by ab T cell-mediated damage. The recovery from hyperglycaemia exhibited by 4/12 TCR-a ¹/mice, in contrast with the high sensitivity of NOD-scid/ scid mice to MD-STZ, indicates, as suggested previously [7], that the DNA repair defect in scid/scid mice may be an important additional determinant in susceptibility to IDDM induced by MD-STZ, and in the absence of ab T cells IDDM is less severe, or transitory.…”

“…The recovery from hyperglycaemia exhibited by 4/12 TCR-a ¹/-mice, in contrast with the high sensitivity of NOD-scid/ scid mice to MD-STZ, indicates, as suggested previously [7], that the DNA repair defect in scid/scid mice may be an important additional determinant in susceptibility to IDDM induced by MD-STZ, and in the absence of ab T cells IDDM is less severe, or transitory. …”

“…Several lines of evidence suggest that the disease is T celldependent: (i) many antibodies reactive with lymphocytes, MHC or adhesion molecules have been found to inhibit STZ-induced insulitis and diabetes: anti-CD3 [1,2], -CD4, -CD8, Thy-1 [3][4][5], -Vb8 [6], -IL-2 receptor [7], -H-2A, H-2E [8][9][10] -LFA-1 [11]; (ii) cytokines are detectable in the pancreas before the onset of overt diabetes [12,13], and disease is inhibitable by treatment with an anti-interferon-gamma (IFN-g) antibody [13]; (iii) STZ has been found to induce the widespread expression of MHC class II [14][15][16][17]; (iv) in some [18], but not all [19], studies MHC congenic mice differ in their susceptibility to STZ-induced IDDM; (v) STZ injection has been reported to induce rat insulinoma cell linespecific cytotoxic T lymphocytes (CTL) [20]; (vi) a variety of immunosuppressant drugs have been found to inhibit disease [21]; (vii) B7.1 transgenic mice have an enhanced susceptibility to disease [22]; (viii) some stocks of athymic (nude) mice have proved relatively resistant to disease induction [23,24]; (ix) resistance to disease can be induced through the intrathymic transplantation of STZ-treated islet cells [25].…”