Animal studies have documented a critical role for
cytokines in cell signaling events underlying
inflammation and
pain associated with tissue injury. While clinical reports indicate an important role of
cytokines in inflammatory
pain, methodological limitations have made systematic human studies difficult. This study examined the utility of a human in vivo bioassay combining microdialysis with multiplex immunoassay techniques for measuring
cytokine arrays in tissue. The first experiment measured
cytokines in interstitial fluid collected from non-inflamed and experimentally inflamed skin (UVB). The effects of noxious heat on
cytokine release were also assessed. The second experiment examined whether anti-hyperalgesic effects of the COX-inhibitor
ibuprofen were associated with decreased tissue levels of the pro-inflammatory
cytokines IL-1 beta and
IL-6. In the first experiment,
inflammation significantly increased
IL-1 beta,
IL-6,
IL-8,
IL-10,
G-CSF, and MIP-1 beta. Noxious heat but not experimental
inflammation significantly increased
IL-7 and
IL-13. In the second experiment, an oral dose of 400 and 800 mg
ibuprofen produced similar anti-hyperalgesic effects suggesting a ceiling effect. Tissue levels of
IL-1 beta and
IL-6 were not affected after the 400mg dose but decreased significantly (44+/-32% and 38+/-13%) after the 800 mg dose. These results support the utility of explored method for tracking
cytokines in human tissue and suggest that anti-hyperalgesic and anti-inflammatory effects of
ibuprofen are at least partially dissociated. The data further suggest that high clinical doses of
ibuprofen exert anti-inflammatory effects by down-regulating tissue
cytokine levels. Explored human bioassay is a promising tool for studying the pathology and pharmacology of inflammatory and
chronic pain conditions.