The hypothesis was tested that alcohol may modulate alveolar macrophage cytokine receptors, thus interfering in lung immune defense mechanisms. Male rats were treated with alcohol either acutely (7 hr continuous intravenous alcohol infusion at a rate of 30 mg/100 g body weight/hr after a priming dose of 175 mg/100 g body weight) or chronically (feeding an alcohol-containing liquid diet for 12-14 weeks). Three hr before killing, the rats received an intravenous injection of Gram-negative bacterial lipopolysaccharide (LPS; Escherichia coli, O26:B6, 100 micrograms/100 g body weight). After anesthesia with sodium pentobarbital, the trachea was cannulated, and the lungs excised and lavaged to obtain alveolar macrophages. The recovered cells were used to measure the binding of recombinant human [125I]tumor necrosis factor-alpha (TNF-alpha) and [125I]interleukin-6 (IL-6). Kd and Bmax were determined at 4 degrees C, thus reflecting only the cell-surface binding sites and their affinity. Two binding sites were detected for both cytokines: high-affinity (Kd1 in the range of 20-110 pM), low-capacity (Bmax1 in the range of 1-13 fmol/10(6) cells), and low-affinity (Kd2 in the range of 0.6-1.3 nM), high-capacity (Bmax2 in the range of 34-100 fmol/10(6) cells). Acute alcohol treatment significantly decreased Bmax1 (39%) and Bmax2 (79%) for TNF-alpha, whereas chronic alcohol feeding abrogated the Bmax1 (Bmax1 = 0), without affecting Bmax2. In the acute group, LPS had an effect similar to that of alcohol. Alcohol administration did not modify the LPS effects. The following changes were monitored for IL-6 binding. Acute alcohol treatment markedly reduced (86%) Bmax2.(ABSTRACT TRUNCATED AT 250 WORDS)