Studies on the Mode of Action of Diphtheria Toxin V. Protein Metabolism in a Guinea Pig Model Simulating Chronic Diphtheritic Toxemia

An experimental model of "chronic" diphtheria intoxication in the guinea pig was developed. Adult guinea pigs, subjected to a regimen of multiple sublethal doses of purified diphtheria toxin (total of 1.4 minimum lethal doses divided equally in four daily doses), developed a toxemia which terminated in death between 6 and 8 days. During an advanced stage of illness, de novo protein synthesis was assessed by in vivo incorporation of tritiated leucine into tissue proteins. With the exception of pancreas and skeletal muscle, protein synthesis in healthy, control and toxin-treated guinea pigs was comparable. The absence of notable impairment of protein synthesis in this experimental situation is discussed in terms of the mode of action of the diphtheria toxin and the pathophysiology of the disease.