Cytokine genotype and phenotype effects on lung function decline in firefighters

OBJECTIVE: We conducted this study to evaluate the association of cytokine genotypes and sputum concentrations on longitudinal decline in lung function in firefighters. METHODS: In 67 firefighters with at least four pulmonary function tests, DNA was analyzed for functional polymorphisms of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-8, IL-10, tumor necrosis factor-alpha (TNF-α) genes, and sputum evaluated for cytokine concentration by ELISA. RESULTS: The annual rate of FEV1 decline was greater in firefighters with TT genotypes at IL-10 (-819) (P = 0.009) and with CT or TT genotypes at IL-1RA (2018) (P = 0.050). These genotypes were not associated with concentrations of sputum cytokine, but increased IL-1RA was associated with a slower rate of FEV1 decline (P = 0.025), as was increased sputum macrophage count (P = 0.002). CONCLUSIONS: Cytokine genotypes were associated with the rate of FEV1 decline but did not alter concentrations of sputum cytokine. Increased sputum IL-1RA may be protective.