Long-term toxicity of modified recombinant human tumor necrosis factor in Macaca mulatta.
OBJECTIVE
To study the long-term toxicity of modified recombinant human tumor necrosis factor (rhTNF-NC) in Macaca mulatta compared with recombinant human tumor necrosis factor (rhTNF).


METHODS
rhTNF-NC 93, 9.3 GU/m2, and rhTNF 62 GU/m2 were injected i.v. daily to 16 Macaca mulatta for 1 month and 10 d, respectively. Hematologic, chemical, urinalysis values, ECG, specific antibody, bone marrow, and pathologic profile of organs were measured.


RESULTS
No more adverse effects of rhTNF-NC were found in spite of anorexia in 4 monkeys and palpebral edema in 2 monkeys of 93 GU/m2 group. Besides, in rhTNF group, the injury of liver and kidneys, the decrease of erythron, the phlebitis, and thrombosis at injection site occurred. Both drugs caused the production of specific antibody.


CONCLUSIONS
No serious adverse effects of rhTNF-NC were found in Macaca mulatta. The toxicity of rhTNF-NC was much lower than that of rhTNF.
Gu
C H
CH
Centre of New Drug Evaluation, Second Military Medical University, Shanghai, China.
Yuan
B J
BJ
Lu
G C
GC
Dai
Z R
ZR
Liu
J P
JP
Zhang
S Y
SY
Zhang
P
P
Jiang
C L
CL
D000818:Animals; D001856:Bone Marrow Examination; D005260:Female; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008253:Macaca mulatta; D008297:Male; D011994:Recombinant Proteins / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha