Effects of chronic alcohol consumption on neutrophilic host defense in rats

Human alcohol abusers have increased vulnerability to infections. It has been hypothesized that one contributing cause of this vulnerability is the detrimental effect of alcohol on neutrophil function. In order to test this hypothesis, we have evaluated the chemotactic responsiveness of the neutrophils of rats (n=12; 7/12 at 150g starting weight/young and 5/12 at 250g starting weight/mature) fed with a 33% chronic alcohol diet (BIO-SERV liquid alcohol diet #F1697/LD'82), with weight-matched pair-fed (n=12) and weight-matched normal ad libitum diet (n=12) rats serving as controls. The differential count for the neutrophils in rats fed with a chronic alcohol diet was low for both young (6.4±0.3%) and mature (7.0±0.2%) rats. These low counts were similar to the neutrophil count of young pair-fed isoenergetic rats (6.5±0.2%), but differed significantly (P<0.001) from mature pair-fed isoenergetic (11.0±0.4%) and normal ad libitum (young: 10.7±0.2%; mature: 10.9±0.8%) controls. In addition, there was a significant presence of band neutrophils in the rats fed with the chronic alcohol diet (n=11/12; 15.0±2.1%), and this differed significantly (P<0.001) from pair-fed (n=5/12; 2.5±0.4%) and normal ad libitum (n=7/12; 2.2±0.3%) controls. Neutrophils isolated from the blood samples of all alcohol diet rats (blood alcohol levels at 359±127 mg/dl range) were viable (trypan-blue exclusion ≥97%); however, these neutrophils were chemotactically non-responsive (2.8±2.3 neutrophils/100x oil field using LPS-endotoxin activated plasma as chemoattractant) and differed significantly (P<0.001) from viable (≥97%) pair-fed (10.3±12.0 neutrophils/100x oil field) and normal ad libitum (26.3±3.0 neutrophils/100x oil field) controls. A detailed analysis revealed a unique and significant (P<0.001) dichotomy in the chemotactic responsiveness in the pair-fed rats (a low chemotactic score of 0.7±1.1 neutrophils/100x oil field for young rats and a normal chemotactic score of 23.5±3.4 neutrophils/100x oil field for mature rats). The limited diet resulting from pair-feeding apparently exerted a significant negative influence (P<0.001) on the chemotactic responsiveness of the young, but not mature, rats. This dichotomy could be explained by the nutritional impact of a pair-fed limiting diet on the young rats which were in an early stage of rapid growth and development. This study presents a mechanism (neutrophilic abnormalities) to explain the vulnerability to infections in chronic alcohol abusers, and identifies a variable in utilizing very young animals for pair-fed control in nutrition and development research.