Cocaine-use disorder and childhood maltreatment are associated with the activation of neutrophils and increased inflammation

Abstract

Background: Cocaine use disorder (CUD) has been associated with early life adversity and activated cellular immune responses. Women are most vulnerable to complications from chronic substance disorders, generally presenting an intense feeling of abstinence and consuming significant drug amounts. Here, we investigated neutrophil functional activities in CUD, including the formation of Neutrophil Extracellular Traps (NETs) and related intracellular signaling. We also investigated the role of early-life stress in inflammatory profiles. Methods: Blood samples, clinical, data, and history of childhood abuse or neglect were collected at the onset of detoxification treatment of 41 female individuals with CUD and 31 healthy controls (HC). Plasma cytokines, neutrophil phagocytosis, NETs, intracellular ROS generation, and phosphorylated protein kinase B (Akt) and mitogen-activated protein kinases (MAPK)s were assessed by flow cytometry. Results: CUD subjects had higher scores of childhood trauma than controls. Increased plasma cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-12, and IL-10), neutrophil phagocytosis, and production of NETs were reported in CUD subjects as compared with HC. Neutrophils of CUD subjects also produced high levels of intracellular ROS and had more activated Akt and MAPKs (p38/ERK), which are essential signaling pathways involved in cell survival and NETs production. Childhood trauma scores were significantly associated with neutrophil activation and peripheral inflammation. Conclusion: Our study reinforces that smoked cocaine and early life stress activate neutrophils in an inflammatory environment.

Unravelling the complex tapestry of addiction: insights from recent research

“…Funchal’s work on the association between CUD, childhood maltreatment, and inflammation reveals the complex interactions between ELS, substance abuse, and immune response. This study not only contributes to our understanding of the biological pathways through which early adversity influences addiction but also points to potential biomarkers for identifying individuals at high risk of substance use disorders (Funchal et al ., 2024).…”