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Cellular Localization and Temporal Elevation of Tumor Necrosis Factor‐α, Interleukin‐1α, and Transforming Growth Factor‐β1 mRNA in Hippocampal Injury Response Induced by Trimethyltin

Abstract: In certain pathologic states, cytokine production may become spatially and temporally dysregulated, leading to their inappropriate production and potentially detrimental consequences. Tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐1, IL‐6, and transforming growth factor‐β (TGF‐β) mediate a range of host responses affecting multiple cell types. To study the role of cytokines in the early stages of brain injury, we examined alterations in the 17‐day‐old mouse hippocampus during trimethyltin‐induced neurodegeneration characterized by neuronal necrosis, microglia activation in the dentate, and astrocyte reactivity throughout the hippocampus. By 24 h after dosing, elevations in mRNA levels for TNF‐α, IL‐1α, IL‐1β, and IL‐6 mRNA were seen. TGF‐β1 mRNA was elevated at 72 h. In situ hybridization showed that TNF‐α and IL‐1α were localized to the microglia, whereas TGF‐β1 was expressed predominantly in hippocampal pyramidal cells. Intercellular adhesion molecule‐1, EB‐22, Mac‐1, and glial fibrillary acidic protein mRNA levels were elevated within the first 3 days of exposure in the absence of increased inducible nitric oxide synthetase and interferon‐γ mRNA. These data suggest that pro‐inflammatory cytokines contribute to the progression and pattern of neuronal degeneration in the hippocampus.