Alcohol and opioid abuse remain endemic issues in the United States and the world at large. In the United States alone alcohol abuse accounts for 178,000 deaths annually, and opioids most recently accounted for 81,806 deaths in 2022. Their deleterious effects on societies worldwide cannot be understated, as they are both leading causes of preventable death. Literature and clinical evaluation demonstrate their effects in short term intoxication as well as long term systemic effects. Alcohol abuse is one of the premier causes of fatty liver disease, an inflammatory process characterized by elevated liver transaminases, ascites, jaundice, altered mental status, eventually resulting in liver or kidney failure without being appropriately addressed. Neurologic sequalae include cerebral stroke, basal ganglia injury, hepatic encephalopathy and cognitive decline resulting from CNS damage. Opioids, including morphine, hydroxycodeine, fentanyl when in excess similarly exert neurologic effects, resulting in drowsiness, euphoria as well as associated hippocampal injury, which can result in amnestic syndromes. A large component of these disease processes is the activation of inflammatory pathways, that damage surrounding cells and tissues through recruitment of cytokines and immune cells. Clinically derived modalities have been developed to measure levels of inflammation. Measurements of erythrocyte sedimentation rate (ESR) and C-Reactive Protein (CRP), an acute phase reactant (APR) are two very common clinically used modalities that can quantify the degree of inflammation. They are by no means the only measures of inflammation, as many other acute phase reactants (APR’s) increase with recruitment of cytokines and immune cells. One such APR is Pentraxin-3 (PTX-3) from the pentraxin family. The pentraxin family includes many acute phase reactants, of which CRP is also a member. They can be found in many cells, regulate inflammation, and are upregulated by cytokines such as Tumour Necrosis Factor-Alpha (TNF-α), a cytokine released by macrophages and monocytes. Through the employment of the in-silico model Ingenuity Pathway Analysis (IPA), we have modeled the biological pathways that ethanol and morphine share with PTX-3. The analysis serves as an assessment of inflammatory processes activated by these two compounds, in addition to the utility of Pentraxin-3 as a biomarker of ethanol/morphine-induced inflammation. The analysis looked at models in macrophages, in various CNS structures such as the hippocampus, amygdala, and overall findings suggest an activating effect of morphine on PTX-3, and an inhibitory effect of ethanol on PTX-3.
December 28, 2025