Possible involvement of IL-12 in reovirus type-2-induced diabetes in newborn DBA/1 mice.
This study extends our previous observations that the reovirus type-2(Reo-2) can induce autoimmune insulitis, which may be mediated by T-helper (Th) 1-dependent mechanisms, resulting in diabetes in newborn DBA/1 mice. In this study mRNA expression for Th1-related cytokines including Th1 and Th2 cytokines in splenic cells was examined by reverse transcriptase polymerase chain reaction (RT-PCR) in relation to the development of insulitis. Furthermore, the effect of monoclonal antibody (MoAb) against interleukin (IL)-12(p40) on the development of insulitis and the mRNA expression in the splenic cells was examined. The mRNA expression for IL-12(p40), IL-18, and interferon (IFN)-gamma, but not IL-5, increased in the spleen in parallel with the development of insulitis. The treatment with MoAb to IL-12(p40) reduced the insulitis with diabetes which was associated with a decrease in the mRNA expression for IL-12(p40), IL-18 and IFN-gamma, and an increase of IL-4 mRNA expression in the spleen. The present study suggested that Th1-dominant systemic immune responses, being responsible for the development of autoimmune insulitis, might be induced by IL-12-induced and IL-18-activated mechanisms.
Hayashi
T
T
Laboratory of Veterinary Pathology, Yamaguchi University, Yoshida, Yamaguchi 753-8515, Japan. hayashi@agr.yamaguchi-u.ac.jp
Morimoto
M
M
Iwata
H
H
Onodera
T
T
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D005260:Female; D007328:Insulin / Q000097:blood; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018165:Orthoreovirus; D012333:RNA, Messenger / Q000096:biosynthesis; D012088:Reoviridae Infections / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D000911:Antibodies, Monoclonal; D016207:Cytokines; D007328:Insulin; D012333:RNA, Messenger; D018664:Interleukin-12