Anticachectin/tumor necrosis factor-alpha antibodies attenuate development of cachexia in tumor models.
C57BL/6 mice bearing either a transplantable methylcholanthrene-induced sarcoma or Lewis lung adenocarcinoma were passively immunized every other day with a rabbit immunoglobulin fraction raised against murine cachectin/tumor necrosis factor-alpha. Mice bearing methylcholanthrene-induced sarcoma developed tumor-associated hypophagia that was attenuated by anticachectin immunoglobulin treatment. In the same tumor-bearing animals, anticachectin treatment also significantly reduced the extent of carcass protein and fat loss, and reduced tumor weight. Mice bearing Lewis lung adenocarcinoma did not develop significant anorexia or carcass lean tissue depletion as tumor growth progressed, but they lost carcass lipid. Treatment of Lewis lung adenocarcinoma bearing mice with anticachectin antibodies diminished the degree of carcass lipid depletion and prevented plasma hypertriglyceridemia. However, in both tumor models, anticachectin treatment did not affect either the development of anemia, hypoalbuminemia or the increase in serum amyloid P concentrations seen with increasing tumor burden. We conclude that an endogenous cachectin response, inhibitable by exogenously administered antibody, contributes to anorexia and to changes in body fat and protein metabolism in these tumor-bearing animals. Neutralizing endogenous cachectin production with antibodies offers the potential to reduce tissue wasting that is frequently associated with neoplastic disease, but it does not appear to affect all of the hematologic and acute phase responses in these murine tumor models.
Sherry
B A
BA
Laboratory of Medical Biochemistry, Rockefeller University, New York, New York 10021.
Gelin
J
J
Fong
Y
Y
Marano
M
M
Wei
H
H
Cerami
A
A
Lowry
S F
SF
Lundholm
K G
KG
Moldawer
L L
LL
D000230:Adenocarcinoma / Q000150:complications / Q000628:therapy; D000818:Animals; D002100:Cachexia / Q000517:prevention & control*; D005260:Female; D006400:Hematocrit; D007116:Immunization, Passive; D008175:Lung Neoplasms / Q000150:complications / Q000628:therapy*; D008748:Methylcholanthrene; D051379:Mice; D012513:Sarcoma, Experimental / Q000150:complications / Q000628:therapy*; D012709:Serum Albumin / Q000032:analysis; D000683:Serum Amyloid P-Component / Q000097:blood; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D012709:Serum Albumin; D000683:Serum Amyloid P-Component; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D008748:Methylcholanthrene