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Secondhand Smoke, Inflammatory Responses, and Glutathione S-Transferase M1: Results of a Randomized Challenge Experiment

de Villiers, T*; Gilliland, F*; Li, Y; Diaz-Sanchez, D

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doi: 10.1097/01.ede.0000276541.58368.22
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Secondhand smoke (SHS) is associated with a spectrum of adverse respiratory effects. We tested the hypothesis that SHS effects are mediated by both allergic and nonallergic cellular and cytokine inflammatory responses. We also examined whether GSTM1 is a determinant of inflammatory responses to SHS.

Material and Methods:

Ragweed allergen-sensitive subjects were challenged intranasally in a single-blind randomized placebo-controlled crossover trial with allergen alone, SHS alone, and combined allergen plus SHS. The allergen and combined challenges were performed at least 6 weeks apart. TNFα, IL-8, and eotaxin levels and eosinophil, neutrophil, lymphocyte, and macrophage counts were measured after each challenge.


Consistent with previous results, SHS enhanced allergic inflammatory responses. For nonallergic inflammatory responses, SHS showed proinflammatory effects, but did not show the same level of enhancement of allergic response. For eosinophils, there was enhancement of allergic response by SHS. Median eosinophil counts after allergen were 0.0 × 105 (range: 0.0–0.5), 0.5 × 105 (range: 0.0–1.5) for SHS alone, and 3.7 × 105 (range: 0.3–14.5) for combined challenge. For neutrophils, there were large responses to allergen alone and SHS alone, but the combined effect was less than additive. Median neutrophil counts after allergen were 11.0 × 105 (range: 2.2–28.7), 9.1 × 105 (range: 4.1–16.2) after SHS, and 12.5 × 105 (range: 3.7–19.3) after combined challenge. The pattern of cytokine responses reflected the cellular responses: eotaxin responses mirrored the SHS enhancement of allergic responses seen with eosinophils and the negative interaction seen with neutrophils was mirrored in IL-8 responses. These patterns were strongly modified by GSTM1 genotype.


These results suggest that SHS effects are mediated by both allergic and nonallergic cellular and cytokine inflammatory responses but the joint effects vary in allergic and nonallergic pathways. GSTM1 plays an important role in SHS exacerbation of both types of inflammatory responses.

© 2007 Lippincott Williams & Wilkins, Inc.