Repeated topical exposure to benzo[a]pyrene and systemic immune effects in rats: Analysis of splenic responses and macrophage function

Abstract

Environmental exposure to benzo[a]pyrene (BaP), a widespread polycyclic aromatic hydrocarbon (PAH) air pollutant, is associated with systemic immunotoxicity. However, the contribution of dermal exposure to systemic immune effects remains insufficiently characterized, despite the skin being a major route of exposure. This study evaluated systemic immune alterations following 10-day epicutaneous BaP exposure in rats at doses reflecting environmental and occupational exposure levels, focusing on hematological parameters, splenic immune responses, and peripheral macrophage function. BaP exposure reduced circulating leukocyte counts and induced mild hepatocellular injury. In the spleen, structural alterations, including congestion, enhanced erythropoiesis, and reduced periarteriolar lymphoid sheath cellularity, were accompanied by decreased frequencies of CD4⁺ and CD8⁺ T cells. Despite this, splenocytes exhibited increased mRNA expression and stimulated production of IFN-γ, IL-17, and IL-10. These changes were associated with increased mRNA for AhR and Cyp1B1, along with activation of antioxidant pathways, characterized by elevated glutathione levels and upregulation of Nrf2 and HO-1, in the absence of increased reactive oxygen species. This was accompanied by reduced basal proinflammatory activity and apoptosis. In contrast, peritoneal macrophages displayed a proinflammatory and functionally activated phenotype, characterized by increased oxidative activity, elevated TNF and IL-6 production, and enhanced bactericidal capacity. These findings are consistent with compartment-specific systemic immunomodulation following dermal BaP exposure and highlight the skin as a relevant route contributing to the systemic immune effects of environmental PAHs.