The Effects of Chronic Ethanol Ingestion and Smoke Exposure on Anti-Pneumococcal Host Defenses
Individuals who abuse alcohol and tobacco are at increased risk for pneumonia caused by Streptococcus pneumoniae (the pneumococcus). Alcohol and cigarette smoke are known to exert immunosuppressive effects on pulmonary defense mechanisms that protect the host from pneumococcal pneumonia. However, the interactive, combined immunosuppressive effects of ethanol (EtOH) ingestion and smoke exposure remain ill defined. To study these effects, we used a rat model that mimics chronic alcohol abuse and smoking. Rats were exposed to smoke generated by 30 reference cigarettes for one hour twice daily for 12 weeks or to room air (sham-exposed). During the last five weeks of exposure, the rats were pair-fed equal volumes of liquid diet containing 0% or 36% EtOH calories. Nasopharyngeal colonization was unaltered by EtOH ingestion and/or smoke exposure. The movement of pneumococci from the rats’ nasopharynx into the lungs was slightly increased by EtOH ingestion, but EtOH did not impair ciliary beating. Smoke exposure reduced pneumococcal movement into the lungs regardless of diet, and this was correlated with a significant increase in ciliary beat frequency. The effect of concurrent smoke exposure and EtOH ingestion on non-neutrophil (PMN)-mediated killing of pneumococci was investigated using an in vivo bactericidal assay. EtOH ingestion significantly decreased the percentage of pneumococci killed within the rats’ lungs. Unexpectedly, this EtOH-induced defect was counteracted by concurrent smoke exposure, even though smoke exposure alone did not increase intrapulmonary pneumococcal clearance. Quantification of the bactericidal proteins lysozyme and lactoferrin in the rats’ lungs did not explain the differences in non-PMN-mediated killing. However, EtOH-fed rats that were sham-exposed exhibited suppressed alveolar macrophage phagocytosis of pneumococci as well as diminished opsonization of the bacteria within their lungs. It is uncertain if smoke exposure increased macrophage phagocytosis due to technical problems with the assay, but concurrent smoke exposure did not exacerbate the EtOH-related decrease in opsonic protein activity. PMN functions also were analyzed in our rat model. Using a similar in vivo bactericidal assay, EtOH ingestion alone was shown to abolish PMN-mediated killing of pneumococci within the lungs. Smoke exposure alone had no effect on this activity, but the addition of smoke exposure to EtOH ingestion restored PMN killing. The differences in bacterial killing were not due to alterations in PMN recruitment to the lungs or PMN phagocytosis of pneumococci. EtOH ingestion alone reduced systemic levels of cytokine-induced neutrophil chemoattractant-1 (CINC-1), which may decrease PMN activation and help explain the absence of pulmonary killing in the EtOH-fed animals. These results indicate that both chronic EtOH ingestion and smoke exposure modulate anti-pneumococcal defenses, but their effects differ significantly in hosts who either abuse alcohol or smoke and those who practice both behaviors.
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