PMID- 8301132 OWN - NLM STAT- MEDLINE DCOM- 19940309 LR - 20071114 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 152 IP - 3 DP - 1994 Feb 1 TI - Intracerebral cytokine mRNA expression during fatal and nonfatal alphavirus encephalitis suggests a predominant type 2 T cell response. PG - 1289-97 AB - Sindbis virus (SV) causes an acute encephalomyelitis in mice. A T cell-dependent inflammatory response is first detected 3 days after infection and includes T cells, B cells, and macrophages. The cytokines produced locally by intrinsic cells of the brain in response to infection and by infiltrating mononuclear cells and their contributions to outcome of infection have not been identified. Semiquantitative reverse transcriptase-PCR was used to evaluate the expression of mRNAs for IL-1 beta, IL-2, IL-4, IL-6, IL-10, TNF-alpha, leukemia inhibitory factor (LIF), and TGF-beta in the brain during fatal and nonfatal SV encephalitis of immunocompetent BALB/cJ and immunodeficient scid/CB17 mice. IL-1 beta and IL-6 mRNAs were detected in uninfected mice before infection and were up-regulated within 24 h. TGF-beta mRNA was also constitutively expressed in uninfected mice. LIF mRNA was occasionally detected in uninfected mice but increased in amounts only in BALB/cJ not scid mice after infection. TNF-alpha, IL-4, and IL-10 mRNAs were not found in uninfected mice but were induced within 24 h and continued to rise through 7 days after infection with substantially higher levels in BALB/cJ than scid mice. These data suggest that intrinsic brain cells produce IL-1, IL-4, IL-6, IL-10, LIF, and TGF-beta mRNAs in response to viral infection. IFN-gamma and IL-2 mRNAs were detected only in BALB/cJ mice and not until 3 days after infection with the initiation of inflammation. IL-4 and IL-10 mRNAs were more persistent and more easily detectable than IL-2 and IFN-gamma mRNAs. These data suggest a predominant type 2 cytokine response in the brain during SV encephalitis. BALB/cJ mice infected with a neurovirulent strain of SV (NSV), had 100% mortality, whereas NSV-infected scid mice developed persistent nonfatal infection. Inflammation was more intense in NSV-infected mice, however, no substantial differences in cytokine mRNA levels were detected when compared with mice with nonfatal SV infection suggesting that the cytokines measured do not in and of themselves lead to fatal central nervous system disease. FAU - Wesselingh, S L AU - Wesselingh SL AD - Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205. FAU - Levine, B AU - Levine B FAU - Fox, R J AU - Fox RJ FAU - Choi, S AU - Choi S FAU - Griffin, D E AU - Griffin DE LA - eng GR - NS07000/NS/NINDS NIH HHS/United States GR - NS18596/NS/NINDS NIH HHS/United States GR - NS29234/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Cytokines) RN - 0 (DNA Primers) RN - 0 (RNA, Messenger) SB - IM MH - Alphavirus Infections/*immunology MH - Animals MH - Base Sequence MH - Brain/*immunology MH - Cytokines/*genetics MH - DNA Primers/chemistry MH - Encephalitis, Arbovirus/*immunology MH - Gene Expression MH - Immunity, Cellular MH - Mice MH - Mice, Inbred BALB C MH - Mice, SCID MH - Molecular Sequence Data MH - RNA, Messenger/genetics MH - Sindbis Virus/immunology/pathogenicity MH - Time Factors EDAT- 1994/02/01 00:00 MHDA- 1994/02/01 00:01 CRDT- 1994/02/01 00:00 PHST- 1994/02/01 00:00 [pubmed] PHST- 1994/02/01 00:01 [medline] PHST- 1994/02/01 00:00 [entrez] PST - ppublish SO - J Immunol. 1994 Feb 1;152(3):1289-97.