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Endogenous cachectin/tumour necrosis factor-alpha production contributes to experimental cancer-associated cachexia
L L Moldawer1, B Sherry, S F Lowry
1Department of Surgery, New York Hospital/Cornell University Medical College, New York.
Cancer Surveys
|January 1, 1989
Summary
The body
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Cancer cachexia involves complex host-mediated changes.
- Cachectin (tumor necrosis factor-alpha) is implicated in these systemic effects.
- Detecting cachectin in cancer patients' serum is challenging with current methods.
Purpose of the Study:
- To explore the role of endogenous cachectin synthesis in cancer-associated host alterations.
- To investigate the production of cachectin by tissue macrophages in tumor-bearing organisms.
- To understand how cachectin and synergistic cytokines contribute to cancer cachexia.
Main Methods:
- Review of existing research lines on cachectin and cancer.
- Analysis of evidence for accelerated macrophage production of cachectin in tumor models.
- Hypothesizing mechanisms for host changes despite undetectable serum cachectin.
Main Results:
- Evidence suggests accelerated cachectin production by tissue macrophages in cancer.
- Serum levels of cachectin remain undetectable in tumor-bearing subjects using current techniques.
- Simultaneous production of synergistic cytokines alongside cachectin is proposed.
Conclusions:
- Endogenous cachectin synthesis by macrophages is a likely contributor to cancer cachexia.
- Host changes in cancer can occur due to tissue-level cytokine activity, not just circulating levels.
- Further research is needed to fully elucidate the role of cachectin and related cytokines in cancer pathophysiology.