Overlap in Interactions of Cadmium and Endocannabinoid Receptors in Downstream Pathways of the Human Immune System

ABSTRACT: Cadmium, a toxic heavy metal with no physiological role in the human body, is encountered mainly through inhalation or ingestion and accumulates due to its slow excretion rate. It negatively impacts health by causing oxidative stress, cellular damage, and apoptosis, especially affecting the kidneys, lungs, and immune system. The endocannabinoid system (ECS), comprising compounds, receptors (CB1, CB2), and enzymes (FAAH, MAGL), regulates immune cell function and homeostasis. The ECS influences various immune cells—including T and B lymphocytes, macrophages, mast cells, dendritic cells, and natural killer cells—mainly by modulating cell proliferation, apoptosis, cytokine secretion, and inflammatory responses. Cadmium disrupts innate immunity by impairing macrophage, neutrophil, mast cell, and NK cell functions, largely through oxidative stress and altered signaling, leading to diminished inflammatory responses and reduced ability to recognize and eliminate threats. In adaptive immunity, cadmium exposure inhibits B and T cell activation and proliferation, induces apoptosis, alters immune memory, and disrupts the balance of helper and cytotoxic T cells, weakening the body’s defense mechanisms. While there is ample evidence for cadmium’s detrimental effects on immune cells and for the ECS’s regulatory role in immunity, direct research on how cadmium affects the ECS specifically is lacking. Current literature suggests possible overlap in the pathways affected by cadmium toxicity and ECS signaling—particularly in the induction of apoptosis and the suppression of immune function—raising the hypothesis that cadmium may modulate immune responses by interacting with endocannabinoid receptors. Further research is needed to clarify these interactions and their implications for immunity.