Acute cigarette smoke exposure alters lung eicosanoid and inflammatory cell concentrations in rabbits

We studied lung clearance of technetium-labeled diethylenetriamine pentaacetic acid ([^99mTc]DTPA), plasma and bronchoalveolar lavage fluid (BALF) concentrations of 6-keto-PGF_la (stable metabolite of prostacyclin, prostaglandin I₂, PGI-J, TxB₂ (stable metabolite of thromboxane A₂, TxA-J, and leukotriene B₄ (LTB₄), and inflammatory cells as indices of lung injury in rabbits exposed to cigarette smoke (CSE). Thirty-one rabbits were randomly assigned to four groups: control sham exposure (SS, n = 6), sham smoke ibuprofen-pretreated (SST, n = 7), CSE (n = 6), and CSE ibuprofen-pretreated (CSE-I, n = 12). Ibuprofen, a cyclooxygenase eicosanoid inhibitor, was administered as a single daily intramuscular injection (25 mg/kg) for 7 d before the experiment. Cigarette or sham smoke was delivered by syringe in a series of 5, 10, 20, and 30 tidal volume breaths with a 15-min counting period between each subset of breaths to determine [^99mTc]DTPA biological half-life (X_1/2). The CSE-I group was retrospectively divided into rabbits who survived the 30-breath subset (CSE-IL, n = 6) and those who died during the 30-breath CSE (CSE-ID, n = 6). In the CSE, CSE-IL, and CSE-ID groups, [^99mTc]DTPA T₂ as well as BALF LTB₄ levels were significantly decreased. Plasma and BALF 6-keto-PGF_la increased in CSE rabbits compared to the other groups. Alveolar macrophages were lower in the CSE-ID rabbits than in the CSE-IL group. CSE and CSE-IL BALF lymphocyte levels were decreased compared to SS values. Our data indicate that acute CSE is associated with significant increases in 6-keto-PGF_la and decreases in LTB₄ as well as a significant reduction in lymphocytes. Furthermore, pre-treatment with ibuprofen before CSE was associated with severe lung injury in half of the rabbits. The severity of lung injury may be related to a combination of a lower number of alveolar macrophages and blockade of lung PGI₂.