Cytokine profile in human skin in response to experimental inflammation, noxious stimulation, and administration of a COX-inhibitor: A microdialysis study

• Published in: Pain (Amsterdam) Vol. 139; no. 1; pp. 15 - 27
• Main Authors: Angst, M.S., Clark, J.D., Carvalho, B., Tingle, M., Schmelz, M., Yeomans, D.C.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 30-09-2008; Lippincott Williams & Wilkins, Inc; Elsevier
• Subjects: Adult; Analgesia; Anti-hyperalgesia; Anti-inflammatory; Biological and medical sciences; Biomarkers - metabolism; Chemokines; Cross-Over Studies; Cyclooxygenase Inhibitor; Cyclooxygenase Inhibitors - administration & dosage; Cytokines; Cytokines - antagonists & inhibitors; Cytokines - biosynthesis; Cytokines - metabolism; Double-Blind Method; Female; Fundamental and applied biological sciences. Psychology; Heat; Hot Temperature - adverse effects; Human; Humans; Hyperalgesia; Ibuprofen; Inflammation; Inflammation Mediators - physiology; Interleukins; Male; Mechanical; Medical sciences; Microdialysis; Microdialysis - methods; Nerve Growth Factor; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Pain Measurement - drug effects; Pain Measurement - methods; Skin; Skin - chemistry; Skin - drug effects; Skin - metabolism; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; Sunburn; Sunburn - drug therapy; Sunburn - metabolism; Ultraviolet B; Vertebrates: nervous system and sense organs; Human; Cytokines; Cyclooxygenase Inhibitor; Anti-hyperalgesia; Inflammation; Nerve Growth Factor; Hyperalgesia; Analgesia; Heat; Microdialysis; Sunburn; Interleukins; Ultraviolet B; Ibuprofen; Mechanical; Skin; Anti-inflammatory; Chemokines; Growth; Interleukin 6; Signal transduction; Pain; Release; Cytokine; Pharmacology; Technique
• ISSN: 0304-3959; 1872-6623
• DOI: 10.1016/j.pain.2008.02.028

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-1β and IL-6. In the first experiment, inflammation significantly increased IL-1β, IL-6, IL-8, IL-10, G-CSF, and MIP-1β. 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-1β and IL-6 were not affected after the 400
mg 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.