Ingested interferon α suppresses Type I diabetes in non-obese diabetic mice

被引:41
作者
Brod, SA
Malone, M
Darcan, S
Papolla, M
Nelson, L
机构
[1] Univ Texas, Hlth Sci Ctr, Dept Neurol, Houston, TX 77225 USA
[2] Univ Texas, Dept Paediat, Div Paediat Endocrinol, Houston, TX USA
[3] Univ Texas, Grad Sch Biomed Sci, Houston, TX USA
[4] Univ S Alabama, Med Ctr, Dept Pathol, Mobile, AL USA
关键词
non-obese diabetic mouse; ingested interferon alpha; interleukin; 4; 10; adoptive transfer;
D O I
10.1007/s001250051056
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Type I diabetes mellitus is a chronic disorder that results from autoimmune destruction of the insulin-producing pancreatic beta cell. The nonobese diabetic mouse is a model of the human autoimmune disease Type I diabetes [1-3]. We have previously shown that ingested type 1 interferon inhibits chronic relapsing experimental autoimmune encephalomyelitis and the adoptive transfer of experimental autoimmune encephalomyelites by T cells, and decreases both antigen-specific and mitogen-induced pro-inflammatory cytokine secretion in this disorder. We therefore tried to determine whether ingested murine interferon alpha inhibits insulinitis and suppresses Type I diabetes mellitus in non-obese diabetic mice. Murine interferon alpha, given daily, decreased islet inflammation and suppressed diabetes. It increased the concanavalin A and ionomycin plus myristic acid palmitic ester-induced production of interleukin 4 and 10 and interferon gamma-secretion in spleen cells from treated mice. Adoptive transfer of unstimulated splenocytes secreting interleukin 4 and interleukin 10 from fed interferon alpha donors suppressed spontaneous diabetes mellitus in recipients. The protective effect of adoptively transferred unstimulated splenocytes shows the presence of ingested interferon alpha-activated regulatory splenic cell populations that may work via increased interleukin 4 or interleukin 10 production. Ingested interferon alpha administered during vulnerable periods in at-risk populations may potentially provide a continuous, convenient, non-toxic and effective treatment for Type I diabetes.
引用
收藏
页码:1227 / 1232
页数:6
相关论文
共 51 条
[1]   Reciprocal action of interferon-gamma and interleukin-4 promotes granulomatous inflammation induced by Rhodococcus aurantiacus in mice [J].
Asano, M ;
Kohanawa, M ;
Minagawa, T ;
Nakane, A .
IMMUNOLOGY, 1996, 88 (03) :394-399
[2]   WHAT CAUSES DIABETES [J].
ATKINSON, MA ;
MACLAREN, NK .
SCIENTIFIC AMERICAN, 1990, 263 (01) :62-&
[3]   INHIBITION OF T-CELL RESPONSES BY ACTIVATED HUMAN CD8+ T-CELLS IS MEDIATED BY INTERFERON-GAMMA AND IS DEFECTIVE IN CHRONIC PROGRESSIVE MULTIPLE-SCLEROSIS [J].
BALASHOV, KE ;
KHOURY, SJ ;
HAFLER, DA ;
WEINER, HL .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 95 (06) :2711-2719
[4]   INTERFERON-INDUCED TRANSFER OF VIRAL RESISTANCE BETWEEN ANIMAL-CELLS [J].
BLALOCK, JE ;
BARON, S .
NATURE, 1977, 269 (5627) :422-425
[6]   COLORECTAL ADMINISTRATION OF HUMAN INTERFERON-ALPHA [J].
BOCCI, V ;
NALDINI, A ;
CORRADESCHI, F ;
LENCIONI, E .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1985, 24 (01) :109-114
[7]   PREVENTION OF DIABETES IN THE NOD MOUSE - IMPLICATIONS FOR THERAPEUTIC INTERVENTION IN HUMAN-DISEASE [J].
BOWMAN, MA ;
LEITER, EH ;
ATKINSON, MA .
IMMUNOLOGY TODAY, 1994, 15 (03) :115-120
[8]   SUPPRESSION OF RELAPSING EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN THE SJL/J MOUSE BY ORAL-ADMINISTRATION OF TYPE-I INTERFERONS [J].
BROD, SA ;
BURNS, DK .
NEUROLOGY, 1994, 44 (06) :1144-1148
[9]   Gut response - Therapy with ingested immunomodulatory proteins [J].
Brod, SA .
ARCHIVES OF NEUROLOGY, 1997, 54 (10) :1300-1302
[10]   Ingested IFN-alpha has biological effects in humans with relapsing-remitting multiple sclerosis [J].
Brod, SA ;
Kerman, RH ;
Nelson, LD ;
Marshall, GD ;
Henninger, EM ;
Khan, M ;
Jin, R ;
Wolinsky, JS .
MULTIPLE SCLEROSIS JOURNAL, 1997, 3 (01) :1-7