Alcohol-induced suppression of lung chemokine production and the host defense response to Streptococcus pneumoniae.

Abstract

Acute alcohol intoxication impairs neutrophil migration in response to intrapulmonary infection with Streptococcus pneumoniae, the most common bacterial cause of pneumonia. Many of the same host defense functions that are impaired in the alcohol-intoxicated host are mechanistically associated with chemokines, a group of proinflammatory molecules that enhance neutrophil adhesion and direct neutrophil migration to sites of inflammation. The purpose of this study was to determine whether alcohol-induced chemokine suppression is responsible for impaired neutrophil recruitment into the lung during infection of the alcohol-intoxicated host. S. pneumoniae was administered (107 colony-forming units) intratracheally 30 min after intraperitoneal injection of 20% alcohol (5.5 g/kg) or saline. Four hours after bacterial challenge, bronchoalveolar lavage fluid (BALF) was collected, and the ability of BALF to induce neutrophil chemotaxis and adhesion molecule expression was measured by using chemotactic and flow cytometric assays. In another experiment, intratracheal challenge was performed by using recombinant macrophage inflammatory protein-2 (MIP-2), and BALF neutrophils were measured. BALF MIP-2 and cytokine-induced neutrophil chemoattractant were decreased by alcohol, and BALF from alcohol-intoxicated animals had decreased chemotactic activity for neutrophils, as well as a decreased ability to up-regulate neutrophil adhesion molecule expression, compared with controls. This decreased chemotactic activity was significantly increased in the alcohol group by repletion of chemokines to control levels. Alcohol also suppressed neutrophil recruitment after intrapulmonary challenge with MIP-2, suggesting that mechanisms other than chemokine suppression contribute to the alcohol-induced effect. At least two mechanisms, suppressed chemokine production and impaired neutrophil adhesion molecule expression, likely work in concert in the alcohol-intoxicated host to impair neutrophil adhesion and migration into the lung during pneumococcal infection. These alterations in neutrophil function likely increase the susceptibility of alcohol-consuming hosts to pneumonia.