Characterization of clinical tolerance to inhaled zinc oxide in naive subjects and sheet metal workers

Clinical tolerance to the acute effects of zinc oxide inhalation develops i n workers during periods of repeated exposure. The aims of this study were to determine whether clinical tolerance is accompanied by a reduction in th e acute pulmonary inflammatory and cytokine responses to zinc oxide exposur e and whether tolerance can be demonstrated in sheet metal workers who chro nically inhale low levels of zinc oxide, Naive (never-exposed) subjects inh aled 5 mg/m(3) zinc oxide on 1 or 3 days and underwent bronchoalveolar lava ge 20 hours after the final exposure. Sheet metal workers inhaled zinc oxid e on 1 day and control furnace gas on another day, Among naive subjects in whom tolerance was induced, bronchoalveolar lavage fluid percent neutrophil s and interleukin-6 (IL-6) levels were significantly decreased compared wit h subjects who underwent only a sing-le exposure, Sheet metal workers were much less symptomatic, but they still experienced a significant increase in plasma IL-6. The results indicate that clinical tolerance to zinc oxide is accompanied by reduced pulmonary inflammation and that chronically exposed sheet metal workers are not clinically affected by exposure to zinc oxide fume at the Occupational Safety and Health Administration Permissible Expos ure Limit. The increase in IL-6 levels observed in the clinically responsiv e, and to a lesser extent, tolerant, states following zinc oxide inhalation is consistent with the dual role of IL-6 as a pyrogen and anti-inflammator y agent.