Gender-related tumor necrosis factor-alpha responses in naïve volunteers with Toll-like receptor 4 polymorphisms exposed in a swine confinement facility

The aim of this work is to better understand the responses of people that are exposed to agricultural organic dust and other factors in modern swine production. We investigated the effects of toll-like receptor 4 (TLR4) genotype and gender on respiratory responses of naïve volunteers (18-28 years) to swine barn exposure. Non-smoking healthy subjects (16 men and 13 women) with TLR4 299 (Asp299Gly) and/or 399 (Thr399Ile) polymorphisms (TLR4 299/399) and age-sex matched subjects with TLR4 wild-type alleles spent 5 h in a nonexposed environment (baseline day) and 5 h in a swine facility (exposure day). The results showed significant decreases between baseline and exposure days in across-shift forced vital capacity (FVC), forced expiratory volume in 1 second (FEV(1)), forced midexpiratory flow rate (FEF(25-75)), and FEV(1)/FVC ratio and in methacholine concentration that reduced FEV1 by 20% (PC(20)) in all groups; however, there were no differences by sex or genotype. Similarly, nasal cytokines, serum cytokines, and blood neutrophil count increased after exposure; in contrast, however, these were influenced by gender. The increase in serum tumor necrosis factor-alpha (TNF-alpha) between baseline and exposure was gender-dependent with male sex associated with a significant increase in the wild-type group and female sex associated with a significant increase in the polymorphic group. These results suggest that for persons exposed to a swine facility, one's immunological response varies with gender as well as TLR4 genotype.