The role of brain cytokines in mediating the behavioral and neuroendocrine effects of intracerebral Mycoplasma fermentans

Raz Yirmiya*, Joseph Weidenfeld, Ohr Barak, Ronit Avitsur, Yehuda Pollak, Ruth Gallily, Avital Wohlman, Haim Ovadia, Tamir Ben-Hur

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Intracerebral administration of Mycoplasma fermentans (MF), a small microorganism that has been found in the brain of some AIDS patients, induces behavioral and neuroendocrine alterations in rats. To examine the role of tumor necrosis factor-α (TNFα) and interleukin-1 (IL-1) in mediating these effects we measured MF-induced expression of TNFα and IL-1β mRNA in various brain regions, and the effects of TNFα synthesis blockers and IL-1 receptor antagonist (IL-1ra) on MF-induced sickness behavior and adrenocortical activation. Intracerebroventricular (i.c.v.) administration of heat- inactivated MF induced the expression of both TNFα and IL-1β mRNA in the cortex, dorsal hippocampus, amygdala, and hypothalamus. Pre-treatment of rats with either TNFα synthesis blockers, pentoxifylline or rolipram, or with IL- 1ra did not attenuate MF-induced anorexia, body weight loss, and suppression of social behavior. However, simultaneous administration of both pentoxifylline and IL-1ra markedly attenuated MF-induced anorexia and body weight loss, but had no effect on the suppression of social behavior. Pre- treatment with pentoxifylline, but not with IL-1ra, significantly attenuated MF-induced corticosterone (CS) secretion. Together, these findings indicate that both TNFα and IL-1 participate, in a complementary manner, in mediating some of the behavioral effects of MF, whereas only TNFα, but not IL-1, is involved in mediating MF-induced adrenocortical activation. We suggest that cytokines within the brain are involved in mediating at least some of the neurobehavioral and neuroendocrine abnormalities that may be produced by MF in AIDS patients.

Original languageAmerican English
Pages (from-to)28-38
Number of pages11
JournalBrain Research
Issue number1-2
StatePublished - 22 May 1999

Bibliographical note

Funding Information:
The authors thank Edna Cohen, Roee Canaan, Dory Freidman, Noya Regev, Jutta Rosenthal, and Anna Itzik for their help in running the experiments. This work was supported by grant 97-204 from the United States–Israel Binational Science Foundation.


  • AIDS
  • Brain
  • Corticosterone
  • Cytokine
  • IL-1ra
  • Interleukin-1
  • Mycoplasma fermentans
  • Pentoxifylline
  • Rolipram
  • Sickness behavior
  • TNFα


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