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Factors influencing the effects of murine cytomegalovirus on the pancreas
Author(s) -
Patricia Price,
Alan G. Baxter,
R.N. Allcock,
John Papadimitriou
Publication year - 1998
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.1998.00314.x
Subject(s) - insulitis , congenic , nod mice , immunology , biology , nod , cytokine , cytomegalovirus , pancreatic islets , antibody , virus , autoimmunity , diabetes mellitus , endocrinology , herpesviridae , islet , viral disease , gene , biochemistry
Background As human cytomegalovirus (HCMV) infections are implicated in insulin‐dependent diabetes mellitus (IDDM), the effects of murine (M)CMV infection of inbred mice on the pancreas are of interest. Results Inflammation and periacinar oedema peaked on day 3 and were replaced by a focal inflammation, but infected cells were rare. The islets were spared in C57BL mice. Insulitis normally seen in non‐obese diabetic (NOD) mice was accelerated, but infected NOD mice did not become glycosuric. Isotypes of total and autoreactive antibodies suggested a shift to a Th1 response (IgG 2a ) in all MCMV‐infected mice. MCMV‐induced pancreatitis was not affected by MHC genes but was similar or less severe in BALB/c mice. As these lack the Cmv1 gene, which provides a protective natural killer (NK) cell response in C57BL congenic mice, the C57BL background may carry a pancreatitis susceptibility gene able to counter NK‐mediated restriction of viral replication. Consistently, congenic mice expressing Cmv1 on a BALB/c background did not display pancreatitis, unless depleted of NK cells. In vivo treatment with soluble cytokine receptors suggested that interleukin 1 (IL‐1) and/or tumour necrosis factor α contribute to acinar necrosis in C57BL mice.