title: Effects of tacrolimus (FK506) on encephalomyocarditic virus-induced diabetes in mice.
abstract: The effects of tacrolimus on insulin-dependent diabetes mellitus (IDDM) induced by the D-variant of encephalomyocarditis virus (D-EMCV) have been investigated. Male BALB/c mice were treated with tacrolimus before viral inoculation, and then were inoculated with 10 plaque forming units (PFU) of DEMCV. The mice continued to be treated with tacrolimus until the animals were sacrificed. D-EMCV-infected mice, which were treated with saline as controls, showed abnormal glucose tolerance test (GTT) values, whereas all infected mice with tacrolimus pretreatment were normal on 7 days-post inoculation (DPI). Histological observations revealed that non-treated tacrolimus D-EMCV-infected mice and which developed diabetes showed severe insulitis in their islets of Langerhans. On the other hand, D-EMCV-infected mice treated with tacrolimus were normal. In D-EMCV-infected mice, viruses in the pancreata were detected at the same level regardless of treatment with tacrolimus or saline. Expressions of TNF-alpha and IFN-gamma mRNA in spleens of tacrolimus-treated D-EMCV-infected mice were lower than that of non-treated tacrolimus DEMCV-infected mice on 7 DPI. The results suggest that tacrolimus suppresses expressions of TNF-alpha and IFN-gamma mRNAs to prevent the onset of D-EMCV-induced IDDM.
authors.affiliation: Faculty of Agriculture, The University of Tokyo, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Yama
authors.forename: Wakako
authors.initials: W
authors.lastname: Nishioka
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Hirokami
authors.forename: Ruka
authors.initials: R
authors.lastname: Setoguchi
authors.forename: Natsumi
authors.initials: N
authors.lastname: Takeyama
authors.forename: Keiichi
authors.initials: K
authors.lastname: Saeki
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Hayashi
authors.forename: Kunio
authors.initials: K
authors.lastname: Doi
authors.forename: Takashi
authors.initials: T
authors.lastname: Onodera
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D018188:Cardiovirus Infections / Q000150:complications* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000517:prevention & control* / Q000821:virology*; D004686:Encephalomyocarditis virus / Q000254:growth & development / Q000302:isolation & purification; D015870:Gene Expression; D005951:Glucose Tolerance Test; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007515:Islets of Langerhans / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010179:Pancreas / Q000473:pathology / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D019562:Viral Load
chemical_list: D001786:Blood Glucose; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016559:Tacrolimus