Small amounts of exogenous IL-4 increase the severity of encephalitis induced in mice by the intranasal infection of herpes simplex virus type 1.
The effect of murine rIL-4 on the development of herpesvirus encephalitis (HSE) in mice infected intranasally with herpes simplex virus type 1 (HSV-1) was investigated. The mortality rates of mice infected with a 0.5 LD50 dose of HSV-1 were greatly increased after the administration of rIL-4 at doses ranging from 0.01 to 1.0 U/mouse 2 h before and 2, 4 and 6 days after the infection. In contrast, survival rates of mice exposed to a 5 LD50 dose of HSV-1 were clearly increased when these mice were treated with anti-IL-4 mAb. Cervical lymph node (CLN) cells and cerebrospinal fluid (CSF) cells from mice with HSE (HSE mice) produced IL-4 in their culture fluids when they were stimulated in vitro with HSV-1 Ag. Increased amounts of HSV-1 infection in mice resulted in the increased production of IL-4 in the culture fluids of local lymphocytes. However, significant amounts of IL-4 were not produced in serum specimens or in culture fluids of spleen cells from HSE mice. IL-4 production in culture fluids of CLN and CSF cells from HSE mice was clearly reduced after treatment of HSE mice with anti-IL-4 mAb. Furthermore, IL-4 production by CLN and CSF cells was greatly enhanced when the cells were prepared from HSE mice previously treated with rIL-4. The IL-4 was mainly produced from CD4+ T cells. These results demonstrate that small amounts of exogenous IL-4 increase the severity of HSE in HSV-1-infected mice through the increased production of IL-4 from local CD4+ T cells.
Ikemoto
K
K
Department of Neurology, Yamaguchi University School of Medicine, Japan.
Pollard
R B
RB
Fukumoto
T
T
Morimatsu
M
M
Suzuki
F
F
D000281:Administration, Intranasal; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001921:Brain / Q000821:virology; D002522:Chlorocebus aethiops; D018792:Encephalitis, Viral / Q000097:blood / Q000134:cerebrospinal fluid / Q000473:pathology*; D006561:Herpes Simplex / Q000097:blood / Q000134:cerebrospinal fluid / Q000473:pathology*; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D007928:Lethal Dose 50; D008198:Lymph Nodes / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology; D018139:Simplexvirus / Q000302:isolation & purification; D013154:Spleen / Q000473:pathology; D018418:Th2 Cells / Q000378:metabolism; D014709:Vero Cells
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D011994:Recombinant Proteins; D015847:Interleukin-4