Hepatic arterial infusion of human recombinant tumor necrosis factor-alpha. An experimental study in dogs.
Local and systemic toxicities associated with hepatic arterial infusion of human recombinant tumor necrosis factor (rTNF) were studied in healthy adult mongrel dogs. The animals received saline containing human serum albumin with or without rTNF (0.02, 0.2, or 2.0 mg/m2). Arteriograms were made, and blood samples were collected for hematologic and biochemical analyses at regular intervals. The dogs were killed at 1, 3, and 7 days postinfusion and complete necropsies were performed. Specimens were obtained from various tissues for histopathologic evaluation. Results indicated that all but the highest dose of rTNF were well tolerated. Severe histopathologic changes were found in the liver, spleen, and kidneys of the animals receiving 2.0 mg/m2 rTNF. In addition, focal tubular degeneration was found in one dog administered 0.2 mg/m2 rTNF. These data suggest that the upper dose limit for hepatic arterial infusion of rTNF is between 0.2 and 2.0 mg/m2 and that renal function should be closely monitored after infusion.
Ohkawa
S
S
Department of Diagnostic Radiology, University of Texas, M. D. Anderson Cancer Center, Houston 77030.
Wright
K C
KC
Mahajan
H
H
Mavligit
G M
GM
Wallace
S
S
D000792:Angiography; D000818:Animals; D001772:Blood Cell Count; D001806:Blood Urea Nitrogen; D003967:Diarrhea / Q000139:chemically induced; D004285:Dogs; D005260:Female; D006499:Hepatic Artery; D006529:Hepatomegaly / Q000139:chemically induced; D007261:Infusions, Intra-Arterial; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D008297:Male; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000633:toxicity
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha