Decreases in macrophage mediated antitumor activity with aging

We have demonstrated that immunotherapy of young (6–10 weeks old), and aged, (greater than 24 months old), tumor bearing mice with biological response modifiers enhanced survival and inhibited tumor growth, while treatment of aged mice had little or no effect. We hypothesized that the antitumor acti...

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Bibliographic Details
Published in:Mechanisms of ageing and development 1995-01, Vol.77 (3), p.169-184
Main Authors: Wallace, Paul K., Eisenstein, Toby K., Meissler, Joseph J., Morahan, Page S.
Format: Article
Language:English
Subjects:
Aging
Aging - physiology
Animals
Antineoplastic agents
Biological and medical sciences
Biological response modifiers
Female
Immunotherapy
Interferon
Interferon-gamma - pharmacology
Interleukin-1 - biosynthesis
Lipopolysaccharides - pharmacology
Macrophage
Macrophage Activation
Macrophages, Peritoneal - physiology
Male
Medical sciences
Mice
Mice, Inbred C57BL
Neoplasms, Experimental - immunology
Neoplasms, Experimental - physiopathology
Nitric Oxide - biosynthesis
Pharmacology. Drug treatments
Tumor Necrosis Factor-alpha - biosynthesis
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Summary:We have demonstrated that immunotherapy of young (6–10 weeks old), and aged, (greater than 24 months old), tumor bearing mice with biological response modifiers enhanced survival and inhibited tumor growth, while treatment of aged mice had little or no effect. We hypothesized that the antitumor activity in young mice was principally mediated by activated macrophages (Mφ) and predicted that the change in aged mice was caused by an intrinsic Mφ defect which develops with advancing age. To directly test our hypothesis, we examined the antitumor activity of resident peritoneal Mφ, purified and activated in vitro with IFN γ plus LPS. Paralleling the results seen in vivo, Mφ from aged mice exhibited reduced antitumor activity in comparison with Mφ from younger mice. Moreover, there was reduced capacity of in vitro activated Mφ from aged mice to produce TNF, IL-1 and nitric oxide, which are critical monokines and effector molecules that have been established to either directly inhibit tumor growth or cause tumor cell destruction. These studies establish that peritoneal Mφ from aged mice have an intrinsic defect which prevents them from fully expressing their antitumor potential.
ISSN:0047-6374
1872-6216
DOI:10.1016/0047-6374(94)01524-P