Cytokines are critical intermediaries of immune and inflammatory responses and present a central role in the pathogenesis of numerous rare diseases. Dysregulated cytokine production and signaling contribute to disease onset, progression, and clinical heterogeneity, particularly in autoinflammatory, autoimmune, genetic, and neurodegenerative disorders. They are synthesized and secreted by numerous cell types, including monocytes, T- and B- lymphocytes, dendritic cells, natural killer cells, endothelial cells, fibroblasts, and epithelial cells. Auto-inflammatory and autoimmune diseases represent two major categories of immune-mediated disorders characterized by dysregulated immune responses. Although traditionally considered distinct, increasing evidence supports a continuum between innate and adaptive immune dysfunction. Auto-inflammatory diseases are driven primarily by aberrations in the innate immune system, without significant participation of antigen-specific T cells or autoantibodies. These conditions are often associated with genetic mutations affecting inflammasome components, leading to excessive activation of inflammatory pathways. Recent advances in molecular immunology have allowed the identification of disease-specific cytokine crosses and facilitated the advance of targeted biological therapies. Future research should therefore focus on identifying reliable biomarkers for treatment stratification, understanding mechanisms of therapeutic resistance, and developing safer and more effective immunomodulatory approaches. Continued progress in cytokine biology and precision immunology is expected to substantially improve outcomes and quality of life for patients with rare autoimmune and autoinflammatory diseases. This review delivers a comprehensive overview of cytokine biology, their involvement in rare diseases, and current and emerging cytokine-targeted therapeutic strategies. Additionally, it highlights the role of cytokines as biomarkers and discusses future perspectives in precision medicine.
Technological advancement and industrialization have significantly increased human exposure to xenobiotics, a diverse group of foreign chemical substances with potential toxic effects. Xenobiotics include pharmaceuticals, pesticides, personal care products, industrial chemicals, and environmental pollutants. The liver, as the primary organ responsible for biotransformation, plays a central role in the detoxification and activation of these compounds. However, metabolic processes may generate reactive intermediates that contribute to hepatocellular injury. This review provides a comprehensive overview of xenobiotic classification, mechanisms of hepatic biotransformation, and the molecular pathways underlying xenobiotic-induced hepatotoxicity. Special emphasis is placed on oxidative stress, reactive metabolite formation, and immune-mediated mechanisms. Clinical manifestations, diagnostic approaches, and current management strategies are also discussed. Understanding these processes is essential for early detection, prevention, and improved therapeutic outcomes in patients with xenobiotic-induced liver injury..