Cigarette Smoke-Induced Cerebral Cortical Interleukin-6 Elevation is not Mediated Through Oxidative Stress

Abstract

The author group has previously established an in vivo subchronic cigarette smoke (CS) exposure rat model, in which the systemic oxidative burden as well as the modulation of local anti-oxidative enzymes in the lung has been demonstrated. Oxidative stress has been shown to induce pro-inflammatory cytokine release, including interleukin (IL)-6 in the airways. In this study, we aimed to investigate the changes in IL-6 production, as well as the oxidative/anti-oxidative responses in the cerebral cortex using the same in vivo model. IL-6 was determined by RT-PCR and western-blot analysis. Local oxidative and anti-oxidative responses were determined by measuring cerebral cortical malondialdehyde (MDA) and advanced oxidation protein product (AOPP) levels, superoxide dismutase (SOD) and catalase activities, and the reduced to oxidized glutathione (GSH/GSSG) ratio. Nitrite level was measured by fluorescent spectrophotometry. Our results demonstrated a significant increase in both IL-6 mRNA and protein levels. Reductions of SOD activity and manganese (Mn)SOD protein level were observed together with the increased level of superoxide measured by chemiluminescent signal, after 56 days of CS exposure. There were no significant changes in the cerebral cortical levels of MDA, AOPP, catalase activity, and the GSH/GSSG ratio. Nitrite level was significantly reduced, together with the decreased protein level of nNOS in the cerebral cortex, after 56 days of CS exposure. Our results suggest that exposure to CS induces IL-6 expression in the cerebral cortex, which is not mediated by the oxidative/anti-oxidative imbalance.

Imaging Biomarkers of the Neuroimmune System among Substance Use Disorders: A Systematic Review

“…Preclinical research indicates that <6 months of tobacco smoke exposure was associated with higher levels of proinflammatory cytokine mRNA expression levels in rodent brains [108, 109] and immunohistochemical markers of microglia and astrocyte activation [110], compared to control animals. Conversely, there is evidence for lower levels of neuroimmune markers in long-term (>1 year) tobacco smoking compared to controls [105, 106].…”

“…Our examination revealed several working hypotheses. First, preclinical studies indicate that acute administration of tobacco smoke [108-110], alcohol [147, 153, 154], methamphetamine/MDMA [52, 210-212], and opioids [223, 227-229] activate the neuroimmune system. These findings have yet to be translated and confirmed in humans.…”

Effect of chronic JUUL aerosol inhalation on inflammatory states of the brain, lung, heart and colon in mice

“…Previous studies have shown that conventional tobacco smoking increases proinflammatory cytokines in the brain, specifically TNFα, IL-1β, IL-6 (16, 17). Therefore, gene expression of these inflammatory cytokines were measured by qPCR in different brain regions of mice exposed to JUUL Mango and JUUL Mint, as well as Air controls for 1 or 3 months.…”

Administration of N-acetylcysteine Plus Acetylsalicylic Acid Markedly Inhibits Nicotine Reinstatement Following Chronic Oral Nicotine Intake in Female Rats

“…In mice, microglial morphology changes in striatal tissues have been reported following chronic treatment with nicotine and undergoing withdrawn, which were associated with the release of pro-inflammatory cytokines and increase in ROS ( Adeluyi et al, 2019 ; Saravia et al, 2019 ). Increased TNFα levels have been reported in the nucleus accumbens of rats during cue-induced nicotine seeking ( Namba et al, 2020 ), and an increased TNFα gene expression has also been described in the prefrontal cortex of nicotine- and cigarette smoke-exposed rats ( Lau et al, 2012 ). It is well established that through the activation and nuclear translocation of the transcription factor NF-κB, TNFα induces the synthesis of various pro-inflammatory cytokines, including IL-6 ( Shimizu et al, 1990 ; Kunsch and Rosen, 1993 ; Ping et al, 1996 ).…”