Acute alcohol intoxication impairs the hematopoietic precursor cell response to pneumococcal pneumonia.

BACKGROUND: Alcohol abuse is associated with an increased incidence and severity of pneumonia. In both the general population and individuals consuming excess alcohol, Streptococcus pneumoniae is the most frequent lung infection pathogen. Alcoholic patients with pneumonia frequently present with granulocytopenia, which is predictive of increased mortality. The mechanisms underlying this impaired granulopoietic response to pneumococcal pneumonia have yet to be elucidated. METHODS: Acute alcohol intoxication was induced in mice 30 minutes before intrapulmonary infection with S. pneumoniae. Bone marrow, lung, and blood samples were collected. Bone marrow cells were also isolated from naïve mice and treated in vitro with plasma from mice infected with S. pneumoniae. RESULTS: Alcohol intoxication impaired the pneumococcal-induced increase in granulocyte recruitment into the alveolar space, decreased bacterial clearance from the lung, and increased mortality. Pneumococcal pneumonia significantly increased bone marrow lineage(-) c-Kit(+) Sca-1(+) (LKS) cell number and colony-forming unit-granulocytes and monocyte (CFU-GM) activity of these cells. Both enhanced proliferation of LKS cells and re-expression of Sca-1 surface protein on downstream progenitor cells bearing lineage(-) c-Kit(+) Sca-1(-) surface markers accounted for the expansion of marrow LSK cells during pneumonia. Alcohol intoxication impaired these 2 mechanisms of LKS cell population expansion and was associated with a relative granulocytopenia during pneumococcal lung infection. CONCLUSIONS: Alcohol inhibits the hematopoietic precursor cell response to pneumonia, which may serve as a mechanism underlying the granulocytopenia and impaired host defense in alcohol abusers with bacterial pneumonia.

Acute alcohol intoxication inhibits the lineage- c-kit+ Sca-1+ cell response to Escherichia coli bacteremia.

Alcohol abuse predisposes the host to bacterial infections. In response to bacterial infection, the bone marrow hematopoietic activity shifts toward granulocyte production, which is critical for enhancing host defense. This study investigated the hematopoietic precursor cell response to bacteremia and how alcohol affects this response. Acute alcohol intoxication was induced in BALB/c mice 30 min before initiation of Escherichia coli bacteremia. Bacteremia caused a significant increase in the number of bone marrow lineage (lin(-))-c-kit(+)Sca-1(+) cells. Marrow lin(-)c-kit(+)Sca-1(+) cells isolated from bacteremic mice showed an increase in CFU-granulocyte/macrophage activity compared with controls. In addition to enhanced proliferation of lin(-)c-kit(+)Sca-1(+) cells as reflected by BrdU incorporation, phenotypic inversion of lin(-)c-kit(+)Sca-1(+)Sca-1(-) cells primarily accounted for the rapid increase in marrow lin(-)c-kit(+)Sca-1(+) cells following bacteremia. Bacteremia increased plasma concentration of TNF-alpha. Culture of marrow lin(-)c-kit(+)Sca-1(+)Sca-1(-) cells with murine rTNF-alpha for 24 h caused a dose-dependent increase in conversion of these cells to lin(-)c-kit(+)Sca-1(+) cells. Sca-1 mRNA expression by the cultured cells was also up-regulated following TNF-alpha stimulation. Acute alcohol intoxication inhibited the increase in the number of lin(-)c-kit(+)Sca-1(+) cells in the bone marrow after E. coli infection. Alcohol impeded the increase in BrdU incorporation into marrow lin(-)c-kit(+)Sca-1(+) cells in response to bacteremia. Alcohol also suppressed the plasma TNF-alpha response to bacteremia and inhibited TNF-alpha-induced phenotypic inversion of lin(-)c-kit(+)Sca-1(+)Sca-1(-) cells in vitro. These data show that alcohol inhibits the hematopoietic precursor cell response to bacteremia, which may serve as one mechanism underlying the impaired host defense in alcohol abusers with severe bacterial infections.

Alcohol abuse, immunosuppression, and pulmonary infection.

Excessive alcohol consumption predisposes the host to a wide range of infectious complications, particularly pulmonary infections. Factors that contribute to the development of pulmonary infections in alcohol-abusing patients include dysfunction of the protective barriers in the respiratory tract, aspiration of oropharyngeal contents, nutritional deficiencies, liver disease, and impairment of host defense mechanisms. This review discusses the complex host-pathogen interactions in the airways with an emphasis on how alcohol consumption adversely affects these mechanisms and predisposes the host to infections. Potential immunomodulatory strategies for enhancing host defense function in alcohol-consuming patients are also discussed.