Traffic-related micro- and nanoplastics (MNPs) from tyre wear are among the largest sources of unintentionally released plastic particles in the air. However, their potential health effects remain understudied. We investigated whether short-term exposure to traffic-related MNPs is associated with systemic immunological changes in healthy adults. Three outdoor sites (stop-and-go high-traffic, highway, urban park) were visited with 23 healthy volunteers for 4-h. Venous blood samples were collected immediately before and after, and the following morning. Plasma cytokine/chemokine levels were determined using an OLINK® Target-48 panel. Expression of maturation marker CD16 and activation markers CD10, CD62L, and CD11b were assessed on granulocytes, and monocytes, using flow-cytometry. On-site traffic-related MNPs within particulate matter with an aerodynamic diameter <10 μm (PM₁₀) were collected using a high-volume sampler, and analyzed using pyrolysis-gas chromatography-mass spectrometry. PM₁₀, ultrafine particles, black carbon, trace metals, and polycyclic aromatic hydrocarbons were also monitored. Linear mixed models were used to determine associations from baseline to post-exposures, adjusting for meteorological covariates. Immediately post-exposure, traffic-related MNPs were positively associated with small increases in EGF, IL7, and MMP1 (5.2–16.9%), though not significant after multiple testing correction. The following morning we found significant false discovery rate (FDR)-corrected downregulation of CXCL9 and IL18 (2.3–8.5%), and negative associations with CD16 (−5%) on granulocytes, and CD11b on monocytes (−25.5%). Short-term exposure to the traffic-related particle mixture, including tyre-wear MNPs, was associated with changes in circulatory cytokines/chemokines, and patterns that might indicate mobilization of immature granulocytes. The delayed associations with cytokine decreases and reduced activation marker expressions could suggests resolution-phase activities, rather than inflammatory responses. © 2026 Published by Elsevier Ltd.

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