Spies CD, Lanzke N, Schlichting U, Muehlbauer S, Pipolo C, von Mettenheim M, Morawietz L, Nattermann H, Sander M (2008): Effects of ethanol on cytokine production after surgery in a murine model of gram-negative pneumonia
Alcohol Clin. Exp. Res. 32 (2): 331-338. Epub 2007 Dec 20.
Rationale: Excessive alcohol consumption and surgery act synergistic with respect to an impaired immune response. The frequency of post-operative infectious complications is 2-5- fold increased in long-term alcoholic patients, leading to prolonged hospital stay. In surgical models IL-6 is considered as marker of tissue destruction, IL-10 as marker of anti-inflammatory immune reactivity.
Objectives: In order to detect to what extent IL-6 and IL-10 levels are affected in the lung tissue by the combination of the both, alcohol exposure and surgical stress, we established a murine model of gram-negative pneumonia, including both parameters.
Methods: 32 female Balb/c mice were pretreated with ethanol (EtOH) at a dose of (3.8 mg/kg body weight) or saline (NaCl) for eight days. At day eight of experiment all mice underwent a median laparotomy. Two days post op mice were either applicated 104 CFU K. pneumoniae or received sham-infection with saline. A total number of 4 groups (EtOH/K. pneumoniae; NaCl/K. pneumoniae; EtOH/Sham-infection, NaCl/Sham-infection) was investigated and a clinical score evaluated. 24hrs later mice were sacrificed; lung, spleen and liver were excised for protein isolation and histological assessment. IL-6 and IL-10 levels were detected by ELISA.
Results: Alcohol exposed mice exhibited a worsened clinical appearance. The histological assessment demonstrated a distinct deterioration of the pulmonary structure in alcohol-treated animals. In the lung IL-6 and IL-10 was significantly increased in alcohol-exposed infected mice compared to saline-treated infected mice. The clinical score correlated significantly with IL-6 (r=0.71; p<0.01) and IL-10 levels (r=0.64; p<0.01) in the lung.
Conclusions: Ethanol treatment in this surgical model led to a more severe pulmonary infection with K. pneumoniae which was associated with more tissue destruction and increased levels of IL-6 and IL-10 and a worsened clinical score.