Acute phase response in toxicity studies. II. Findings in beagle dogs injected with endotoxin or subjected to...

Occurrence of characteristic transient changes in WBC counts and fibrinogen values in beagle dogs subjected to single-dose toxicity studies was pointed out in the previous survey (Hoshiya et al., 2001). These changes were thought to belong to the category of "Acute Phase Response (APR)". The purpose of the present study is to compare the APR found in the single-dose toxicity studies surveyed in our previous report with those experimentally produced by intravenous injection of 1 microgram/kg endotoxin (Experiment 1), and surgical treatment (Experiment 2) (intravenous indwelling catheterization). The animals used in Experiment 2 were intravenously injected with 1 microgram/kg endotoxin 2 weeks after the operation (Experiment 3), and the results were compared with those of Experiments 1 and 2. Each experimental group consisted of 5 dogs, and clinical, hematological and blood chemical examinations were performed. Essentially the same changes were observed in response to the intravenous injection with endotoxin and the surgical operation for intravenous indwelling catheterization in beagle dogs. The most remarkable changes common to both treatments were transient increases in the fibrinogen values and WBC counts during the 2 days from Day 1 to Day 2 of the treatment. These changes were preceded by decreases in WBC counts and fibrinogen in Experiments 1 and 3. Increased erythrocyte sedimentation rates were recorded in parallel with the increase in fibrinogen. The results obtained in the present study were similar to those found in dogs treated with various xenobiotic substances in our laboratory. These changes due to different causes were thought to belong to the category of "APR" with the same biological significance as a non-specific defense mechanism.