Factors influencing the effects of murine cytomegalovirus on the pancreas.
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 Th 1 response (IgG2a) 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 Cmvl 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 alpha contribute to acinar necrosis in C57BL mice.
Price
P
P
Royal Perth Hospital, Perth, Australia. pprice@cyllene.uwa.edu.au
Baxter
A G
AG
Allcock
R N
RN
Papadimitriou
J M
JM
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D003587:Cytomegalovirus / Q000472:pathogenicity* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000821:virology*; D005260:Female; D006801:Humans; D006942:Hypergammaglobulinemia / Q000473:pathology / Q000821:virology; D007375:Interleukin-1 / Q000502:physiology; D007515:Islets of Langerhans / Q000473:pathology* / Q000821:virology; D007694:Killer Cells, Natural / Q000276:immunology; D008099:Liver / Q000473:pathology* / Q000821:virology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D009336:Necrosis; D010179:Pancreas / Q000473:pathology* / Q000821:virology; D010195:Pancreatitis / Q000473:pathology / Q000821:virology; D017472:Receptors, Interleukin-1 / Q000008:administration & dosage / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014779:Virus Replication
D001323:Autoantibodies; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha