Pulmonary infection with Pneumocystis carinii, an opportunistic pathogen, is associated with a variety of immunosuppressive states, Including human immunodeficiency virus infection. We hypothesized that alcohol ingestion might compromise host defenses against this pathogen and, in an immunocompromised host, increase the severity of infection. This hypothesis was tested in both acute and chronic ethanol‐treated normal and CD4⁺ T‐cell‐depleted mice challenged with P. carinii organisms.

Normal and CD4⁺ T‐cell‐depleted mice were given an intraperitoneal injection of ethanol or saline 0.5 hr before P. carinii challenge and killed 3 hr later for bronchoalveolar lavage. Acute alcohol treatment decreased significantly tumor necrosis factor (TNF) activity and the number of polymorphonuclear leukocytes (PMNLs) recovered in the lavage in response to the pathogen. Depletion of CD4⁺ T‐cells did not potentiate the effect of alcohol on the early inflammatory response to the pathogen any further. In normal animals, in vivo interferon (IFN)‐γ pretreatment augmented significantly the P. carinii‐ stimulated lung TNF response and PMNL recruitment. However, IFN‐γ pretreatment prevented the alcohol‐induced suppression of TNF secretion without affecting the PMNL recruitment. The effect of chronic alcohol consumption on the severity of infection was studied in long‐term, alcohol‐fed normal and CD4⁺‐depleted mice challenged with P. carinii organisms. Lung histopathology showed that P. carinii infection was present in >60% of the alcohol‐fed mice and in none of the controls. Also, a significantly higher number of PMNLs were recovered in the lavage fluid of alcohol‐fed mice with persistent infection. There was no difference in lavage fluid and cell culture supernatant TNF and reactive nitrogen intermediates release between the two groups. CD4⁺ T‐cell depletion did not alter significantly the effect of alcohol on any of the aforementioned parameters.

We conclude that chronic alcohol ingestion alone induces immunosuppression sufficient to permit pulmonary infection with P. carinii. One possible mechanism for the adverse effects of alcohol on host defenses against P. carinii may be through suppressed host release of cytokines including TNF‐α and IFN‐γ.