Inflammatory Effects of Co-Exposure to Heavy Metals (Cd and Pb) and Respiratory Viruses (229E, OC43, and H3N2) on IL-6 and IL-8 Responses in U87 Glioblastoma Cells

Abstract

Co-exposure to heavy metals and viruses can pose threats to cellular health by increasing cytotoxicity and inflammatory cytokine expression. We aimed to elucidate the interactions between these factors inhuman glioblastoma cells (U87). U87 cells were exposed to influenza A virus (H3N2), coronaviruses OC43 and 229E, and heavy metals Cd and Pb. Cell viability and cytotoxicity were assessed through WST-8 and Lactate Dehydrogenase (LDH) assays. The combined effect of these viruses and metals on Interleukin (IL)-6 and IL-8 inflammatory responses was examined. A high Multiplicity Of Infection (MOI) significantly reduced cell viability, with 0.1 MOI identified as optimal for mild infections. At high MOI levels, 229E and OC43 significantly reduced cell viability, whereas H3N2 caused severe cytotoxicity while preserving cell viability. Elevated LDH levels confirmed cell damage, with OC43 inducing robust IL-8 responses, H3N2 causing moderate IL-6 and IL-8 responses, and 229E triggering a weak IL-6 response. Co-exposure with Cd increased IL-6 and IL-8 levels, indicating pro-inflammatory effects, whereas co-exposure with Pb suppressed IL-8 production. The IL-6 level consistently remained below 800 pg/mL. Conversely, the IL-8 level, which peaked following viral infection, was reduced to below 3000 pg/mL with metal co-exposure. Our findings can aid in formulating healthcare and environmental strategies.