Allergy and automobile pollution: experiments on humans

The increase in allergic airways disease in industrialized countries has be en linked ro particulates fr om fossil fuel combustion. We have employed hu man sl stems to investigate the effects of diesel exhaust particles (DEP) a nd the chemicals they contain upon allergic inflammation. We have shown tha t following nasal challenge of subjects DEP can enhance mucosal IRE product ion and induce an inflammatory response characterized by cell influx and in creased production of chemokines and cytokines in the nasal mucosa. In comb ination with allergen, DEP can enhance local antigen specific IgE productio n, and drive in vivo isotype switch to IgE. These results can be duplicated bi phenanthrene, an important pol! aromatic hydrocarbon found in DEP. Low doses of allergen will synergise with DEP to initiate IL-4 secretion fr-om CD117(+) cells in the nasal mucosa thereby skewing the subsequent response toward a Th2 pattern. In addition, they carl synergize with a neoantigen to drive primary sensitization. One potential mechanism fur these effects is the enhancement of the role of macrophages as antigen presenting cells. Thu s DEP can act as mucosal adjuvants at the cellular and molecular level and thus may cause both allergic sensitization and exacerbation.