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Related Experiment Videos

Physiological effects of CNTF-induced wasting

J T Henderson1, B J Mullen, J C Roder

  • 1Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

Cytokine
|October 1, 1996
PubMed
Summary

Systemic administration of Ciliary Neurotrophic Factor (CNTF) causes severe wasting and death in mice by inducing rapid tissue catabolism. These cachectic effects occur independently of other cytokines.

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Area of Science:

  • Biochemistry
  • Physiology
  • Immunology

Background:

  • Ciliary Neurotrophic Factor (CNTF) is known to affect neuronal and glial survival.
  • Previous studies indicated CNTF induces cachectic effects and acute phase proteins at low concentrations (< or = 10 ng/ml).
  • These effects were independent of other cytokine family members.

Purpose of the Study:

  • To elucidate the specific physiological effects of systemic CNTF administration on somatic tissues.
  • To investigate the consequences of sustained CNTF secretion in vivo.

Main Methods:

  • Mice were implanted with C6 glioma cells engineered to secrete CNTF.
  • Control groups received parental C6 cells or cells expressing a non-secreted CNTF form.
  • Physiological parameters including tissue mass, blood composition, and immune cell populations were monitored.

Main Results:

  • CNTF-secreting C6 glioma cells induced rapid catabolism of adipose and skeletal muscle tissue.
  • Depressed glucose and triglyceride levels, elevated red blood cell counts, gallbladder hypertrophy, and thymic atrophy were observed.
  • A disproportionate loss of CD4+/CD8+ T cells occurred, leading to cachectic wasting and death within 7-10 days.
  • Control groups showed no significant effects.

Conclusions:

  • Systemic CNTF induces profound cachectic wasting and mortality through direct physiological effects on somatic tissues.
  • These findings highlight the potent biological activity of CNTF and its implications for therapeutic applications.
  • The study underscores the importance of considering CNTF's systemic effects in vivo.

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