EXPRESSION OF TUMOR NECROSIS FACTOR-A AND INTERLEUKIN-6 CELL-SURFACE RECEPTORS OF THE ALVEOLAR MACROPHAGE IN ALCOHOL-TREATED RATS

The hypothesis was tested that alcohol may modulate alveolar macrophage cytokine receptors, thus interfering in rung 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 mu g/100 g body weight). After anesthesia with sodium pentobarbital, the trachea was cannutated, and the lungs excised and lavaged to obtain alveolar macrophages. The recovered cells were used to measure the binding of recombinant human [I-125]tumor necrosis factor-alpha (TNF-alpha) and [I-125]interleukin-6 (IL-6). K-d and B-max 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 (K-d1 in the range of 20-110 pM), low-capacity (B-max1 in the range of 1-13 fmol/10(6) cells), and low-affinity (K-d2 in the range of 0.6-1.3 nM), high-capacity (B-max2 in the range of 34-100 fmol/10(6) cells). Acute alcohol treatment significantly decreased B-max1 (39%) and B-max2 (79%) for TNF-alpha, whereas chronic alcohol feeding abrogated the B-max1 (B-max1 = 0), without affecting B-max2. 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%) B-max2. LPS administration to saline-infused group increased K-d1 (122%) and B-max1 (197%), and significantly diminished (72%) B-max2. These effects of LPS were not altered by alcohol administration, with the exception of K-d1, which was decreased (43%) by LPS administration to acutely, alcohol-intoxicated rats. In the chronic treatment group, alcohol feeding increased B-max2 (426%), an effect that was not modified by LPS injection. These data suggest that: (1) both acute and chronic alcohol administration to rats differentially affects the alveolar macrophage cell-surface receptors for TNF-alpha and IL-6, and (2) alcohol-induced alterations in these two cytokine receptors may in part mediate alcohol effects on lung immune defense.