Inflammation Research

, Volume 62, Issue 5, pp 527–535 | Cite as

Tetramethylpyrazine decreases hypothalamic glutamate, hydroxyl radicals and prostaglandin-E2 and has antipyretic effects

  • Chin-Hong Chang
  • Wu-Tein Huang
  • Cheng-Hsing Kao
  • Sheng-Hsien Chen
  • Cheng-Hsien Lin
Original Research Paper



We studied the effects of tetramethylpyrazine (TMP) on the fever, increased plasma levels of tumor necrosis factor-α (TNF-α) and increased hypothalamic levels of glutamate, hydroxyl radicals and prostaglandin-E2 (PGE2) induced by lipopolysaccharide (LPS).

Materials and methods

The microdialysis probes were stereotaxically and chronically implanted into the hypothalamus of rabbit brain for determining extracellular levels of glutamate, hydroxyl radials, and PGE2. In addition, both the body core temperature and plasma levels of TNF-α were measured.


All the body core temperature, plasma levels of TNF-α, and hypothalamic levels of glutamate, hydroxyl radicals, and PGE2 were up-graded by an intravenous dose of LPS (2 μg/kg). Pretreatment with intravenous TMP (10–40 mg/kg) or intracerebroventricular TMP (130 μg in 20 μl per animal) 1 h before LPS administration significantly attenuated the LPS-induced fever as well as the increased hypothalamic levels of glutamate, hydroxyl radicals, and PGE2. LPS-induced fever could also be attenuated by intravenous or intracerebroventricular TMP 1 h after LPS injection.


TMP preconditioning may cause its antipyretic action by reducing plasma levels of TNF-α as well as hypothalamic levels of glutamate, hydroxyl radicals, and PGE2 in rabbits.


Fever Tetramethylpyrazine Antipyresis Hypothalamus Glutamate Hydroxyl radicals Prostaglandin-E2 



This work was supported in part by the National Science Council (Taipei, Taiwan, China) NSC 96-2314-B-384-002 and NSC 96-2314-B-384-003-MY3 and the Department of Health of Republic of China ODH 99-TD-B-111-003 Center of Excellence for Clinical Trial and Research in Neuroscience.

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Springer Basel 2013

Authors and Affiliations

  • Chin-Hong Chang
    • 1
    • 2
  • Wu-Tein Huang
    • 2
  • Cheng-Hsing Kao
    • 1
  • Sheng-Hsien Chen
    • 3
    • 4
  • Cheng-Hsien Lin
    • 5
  1. 1.Department of SurgeryChi Mei Medical CenterTainanTaiwan
  2. 2.Department of Recreation and Health Care ManagementChia-Nan University of Pharmacy and ScienceTainanTaiwan
  3. 3.Department of Obstetrics and GynecologyChi Mei Medical CenterTainanTaiwan
  4. 4.Department of BiotechnologySouthern Taiwan University of Science and TechnologyTainanTaiwan
  5. 5.Department of Medical ResearchChi Mei Medical CenterTainanTaiwan

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