title: Increased serum IL-6 level time-dependently regulates hyperalgesia and spinal mu opioid receptor expression during CFA-induced arthritis.
abstract: Interleukin (IL)-6 is known to cause pro- and anti-inflammatory effects during different stages of inflammation. Recent therapeutic investigations have focused on treatment of various inflammatory disorders with anti-cytokine substances. As a result, the aim of this study was to further elucidate the influence of IL-6 in hyperalgesia and edema during different stages of Complete Freund's Adjuvant (CFA)-induced arthritis (AA) in male Wistar rats. AA was induced by a single subcutaneous injection of CFA into the rats' hindpaw. Anti-IL-6 was administered either daily or weekly during the 21 days of study. Spinal mu opioid receptor (mOR) expression was detected by Western blotting. Daily and weekly treatment with an anti-IL-6 antibody significantly decreased paw edema in the AA group compared to the AA control group. Additionally, daily and weekly anti-IL-6 administration significantly reduced hyperalgesia on day 7 in the AA group compared to the AA control group; however, there were significant increases in hyperalgesia in the antibody-treated group on days 14 and 21 compared to the AA control group. IL-6 antibody-induced increases in hyperalgesia on the 14thand 21stdays after CFA injection correlated with a time-dependent, significant reduction in spinal mOR expression during anti-IL-6 treatment. Our study confirmed the important time-dependent relationship between serum IL-6 levels and hyperalgesia during AA. These results suggest that the stages of inflammation in AA must be considered for anti-hyperalgesic and anti-inflammatory interventions via anti-IL-6 antibody treatment.
authors.affiliation: Physiology Department, Neuroscience Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: E
authors.initials: E
authors.lastname: Tekieh
authors.affiliation: Physiology Department, Neuroscience Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Jalal
authors.initials: J
authors.lastname: Zaringhalam
authors.affiliation: Physiology Department, Neuroscience Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: H
authors.initials: H
authors.lastname: Manaheji
authors.affiliation: Cellular and Molecular Department, Neuroscience Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: N
authors.initials: N
authors.lastname: Maghsoudi
authors.affiliation: Cellular and Molecular Department, Neuroscience Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: B
authors.initials: B
authors.lastname: Alani
authors.affiliation: Physiology Department, Neuroscience Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: H
authors.initials: H
authors.lastname: Zardooz
keywords: CFA; Interleukin-6; arthritis; hyperalgesia; inflammation