Sex Differences in Inflammation Responses to Stress and Traffic-Related Air Pollution in rats

Background: Traffic-related air pollution (TRAP) is associated with cardiovascular morbidity and mortality. Epidemiologic research reveals stronger impacts of air pollution on cardiovascular disease risk among individuals exposed to chronic stressors such as violence and poverty. This study aims to investigate the effects of initial stress followed by combined stress and air pollution exposure on inflammatory biomarkers. Methods: Thirteen weeks old Sprague Dawley rats of both sexes were subjected to either no stress or chronic mild unpredictable stress (CMUS, random order of strobe light, loud noise, crowding, shaker, cage tilting, and no bedding) twice daily for three weeks. On weeks 2 and 3, some rats were exposed to real-time non-transformed TRAP from the Caldecott Tunnel. Each week, plasma samples were collected from the abdominal aorta and markers of inflammatory response were determined with Bio-Rad Rat Cytokine 23-Plex Assay (n=12, 29, and 30 for week 1, 2 and 3, respectively). Results: After one week of CMUS, IL-1β and MIP-1α levels were lower in females but not in males (2-way ANOVA, p<0.05, CMUS x sex interaction). One week of TRAP exposure did not change any of the 23 cytokines regardless of prior stress experience, albeit a trend for lower cytokine levels in some cytokines in the CMUS+TRAP male rats. However, two weeks of TRAP exposure resulted in significant reduction in most of the cytokines in males but not in females (2-way ANOVA, p<0.05, exposure x sex interaction), including cytokines with direct or indirect anti-inflammatory activities (G-CSF, IL-4, IL-10, IL-13, M-CSF) and those with pro-inflammatory activities (IL-1a, IL-2, IL-5, IL-12, IL-17, IFN-γ, TNF-α, MIP-3α). The reductions in the cytokine levels were not modified by prior stress experience. Conclusion: While females had a couple of reduced pro-inflammatory cytokines in response to stress, males had significantly reduced cytokines with pro-inflammatory and anti-inflammatory activities. These data suggest that 1) males and females may have different inflammatory responses to stress and TRAP, 2) TRAP exposure had greater impact in the males, and 3) TRAP can evoked complicated inflammatory responses that involves both pro-inflammatory and anti-inflammatory cytokine productions. Support: R01ES033472-01A1 & P30 ES023513 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.