Inflammation is a primary pathogenic pathway in a wide
range of diseases, including rheumatoid arthritis, Crohn’s
disease, cardiovascular disease, and neuropsychiatric
disorders. To study the effect of compounds that target
inflammatory pathways in the early phases of drug
development, CHDR has developed a series of in vivo, ex vivo,
and in vitro tools to induce inflammation in healthy subjects
and cells

Highlights

  • LPS challenge (in vivo and ex vivo)
  • Histamine challenge - derm
  • Imiquimod challenge – derm
  • Battery of TLR-challenges (ex vivo)
  • Vaccination-based (in vivo)

LPS Challenge

  • Inflammatory cellular pathways downstream of TLR4 (Toll-like receptor 4) can be activated and measured in vitro using blood samples obtained from healthy volunteers. 
  • The in vivo LPS challenge is a safe method for obtaining valuable informative regarding the effects of antiinflammatory compounds in healthy subjects. 
  • The in vivo LPS challenge can also be used to study specific aspects of the inflammatory response, including the vascular endothelium. 
  • CHDR has also developed ex vivo challenges and biomarkers for studying a variety of inflammatory pathways.

LPS challenge 

Histamine Challenge

Measurement of the histamine-induced skin reaction is a well established method to assess the potency and duration of action of compounds such as histamine receptor antagonists or anti-inflammatory drugs. In the histamine skin prick test, 4 increasing doses (0.1, 0.4, 1.6, and 6.4 μg) of histamine are injected intradermally in the back using an automatic intradermal injector. Intradermal injection of histamine results in the induction of an allergic skin response, the wheal-and-flare reaction. A clear dose – response is observed when administering histamine intradermally

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