PMID- 19845729 OWN - NLM STAT- MEDLINE DCOM- 20100419 LR - 20240409 IS - 1528-1167 (Electronic) IS - 0013-9580 (Print) IS - 0013-9580 (Linking) VI - 51 IP - 3 DP - 2010 Mar TI - Innate but not adaptive immune responses contribute to behavioral seizures following viral infection. PG - 454-64 LID - 10.1111/j.1528-1167.2009.02390.x [doi] AB - PURPOSE: To examine the role of innate immunity in a novel viral infection-induced seizure model. METHODS: C57BL/6 mice, mouse strains deficient in interleukin (IL)-1RI, IL-6, tumor necrosis factor (TNF)-RI, or myeloid differentiation primary response gene 88 (MyD88), or transgenic mice (OT-I) were infected with Theiler's murine encephalomyelitis virus (TMEV) or were mock infected. Mice were followed for acute seizures. Tissues were examined for neuron loss, the presence of virus (viral RNA and antigen), perivascular cuffs, macrophages/microglia, and gliosis, and mRNA expression of IL-1, TNF-alpha, and IL-6. RESULTS: IL-1 does not play a major role in seizures, as IL-1RI- and MyD88-deficient mice displayed a comparable seizure frequency relative to controls. In contrast, TNF-alpha and IL-6 appear to be important in the development of seizures, as only 10% and 15% of TNF-RI- and IL-6-deficient mice, respectively, showed signs of seizure activity. TNF-alpha and IL-6 mRNA levels also increased in mice with seizures. Inflammation (perivascular cuffs, macrophages/microglia, and gliosis) was greater in mice with seizures. OT-I mice (virus persists) had a seizure rate that was comparable to controls (no viral persistence), thereby discounting a role for TMEV-specific T cells in seizures. DISCUSSION: We have implicated the innate immune response to viral infection, specifically TNF-alpha and IL-6, and concomitant inflammatory changes in the brain as contributing to the development of acute seizures. This model is a potential infection-driven model of mesial temporal lobe epilepsy with hippocampal sclerosis. FAU - Kirkman, Nikki J AU - Kirkman NJ AD - Department of Pathology, University of Utah, Salt Lake City, Utah 84132, USA. FAU - Libbey, Jane E AU - Libbey JE FAU - Wilcox, Karen S AU - Wilcox KS FAU - White, H Steve AU - White HS FAU - Fujinami, Robert S AU - Fujinami RS LA - eng GR - R01 NS065714/NS/NINDS NIH HHS/United States GR - R01 NS065714-01A1/NS/NINDS NIH HHS/United States GR - NS065714/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20091020 PL - United States TA - Epilepsia JT - Epilepsia JID - 2983306R RN - 0 (Antigens, Differentiation) RN - 0 (Gadd45b protein, mouse) RN - 0 (Interleukin-6) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Animals MH - Antigens, Differentiation/genetics/immunology MH - Behavior, Animal/physiology MH - Brain/immunology/pathology MH - Cardiovirus Infections/*immunology/pathology/virology MH - Disease Models, Animal MH - Epilepsy, Temporal Lobe/immunology MH - Gliosis/immunology/pathology MH - Hippocampus/immunology/pathology MH - Immunity, Innate/*immunology MH - Interleukin-6/immunology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mice, Transgenic MH - Reverse Transcriptase Polymerase Chain Reaction MH - Seizures/etiology/*immunology/pathology MH - Theilovirus/*immunology MH - Tumor Necrosis Factor-alpha/deficiency/*genetics/immunology PMC - PMC3046460 MID - NIHMS271199 COIS- Disclosure of Conflict of Interest: We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. The authors have no conflict of interest to disclose. EDAT- 2009/10/23 06:00 MHDA- 2010/04/20 06:00 PMCR- 2011/03/01 CRDT- 2009/10/23 06:00 PHST- 2009/10/23 06:00 [entrez] PHST- 2009/10/23 06:00 [pubmed] PHST- 2010/04/20 06:00 [medline] PHST- 2011/03/01 00:00 [pmc-release] AID - EPI2390 [pii] AID - 10.1111/j.1528-1167.2009.02390.x [doi] PST - ppublish SO - Epilepsia. 2010 Mar;51(3):454-64. doi: 10.1111/j.1528-1167.2009.02390.x. Epub 2009 Oct 20.