Immunomodulatory and Cytotoxic Properties of Enniatin B1 in Porcine Alveolar Macrophages

This study investigates the immunomodulatory effects of Enniatin B1 (ENNB1), an emerging mycotoxin, on porcine alveolar macrophages (PAMs), a species-specific model relevant to human innate immunity. PAMs were exposed to increasing ENNB1 concentrations (0.5-6 μM) over 6, 24, and 48 h. Results showed a biphasic response: ENNB1 initially enhanced cell viability and induced upregulation of pro- and anti-inflammatory cytokines (e.g., IL-1β, IL-6, IL-10, TNF-α), COX enzymes, and antioxidant gene GPX-2. However, prolonged exposure caused downregulation of these markers and reduced cell viability, indicating cytotoxic and immunosuppressive effects. The temporal and concentration-dependent responses suggest that ENNB1 modulates macrophage function by altering the immune response, with early immune activation followed by immune impairment. These findings provide novel insights into ENNB1's potential to alter immune homeostasis and highlight the need for further toxicological studies for a correct evaluation of the risk.