title: The effect of interleukins 27 and 35 and their role on mediating the action of insulin Like Growth Factor -1 on the inflammation and blood flow of chronically inflamed rat knee joint.
abstract: BACKGROUND
  Previous studies have shown that some cytokines mediate the effect of IGF-1 on inflammation and also association between IGF-1 and vascular endothelial dysfunction. Due to the discrepancies in the inflammatory and anti-inflammatory roles of IL-27 and IL-35, the effects of these cytokines and their IGF-1-mediating role were investigated regarding chronic joint inflammation and synovial blood flow.
  
  
  METHODS
  Male rats were divided into two main groups of histopathology (n=80) and blood flow (n=72). These were further divided into ten subgroups of control, vehicle, IGF-1, IL-27, IL-35, their antagonists, IGF-1+IL-27 antagonist, and IGF-1+IL-35 antagonist. Inflammation was induced by intra-articular injection of complete Freund adjuvant. Two weeks later (in order to induce chronic inflammation), vehicle or drugs were injected into the joint space every other day until day 28, on which inflammatory indices were assessed histopathologically. In the second subgroups, vehicle or drugs were administered by super-fusion on day 28 and their effects on the joint blood flow (JBF, laser Doppler perfusion method) and the systemic blood pressure were assessed.
  
  
  RESULTS
  Endogenous IL-27 and IL-35 had inflammatory roles and IGF-1 had no effect. IL-27 and IL-35 antagonists had the highest anti-inflammatory and anti-angiogenesis effects and these effects were inhibited by IGF-1. Total inflammation score was 4.5 ± 0.42, 3.50 ± 0.5, 2.25 ± 0.45 and 1.50 ± 0.42 for vehicle, IGF-1 antagonist, IL-27 antagonist and IL-35 antagonist respectively. A significant increase was induced in JBF by IGF-1 antagonist and combination of IGF-1+IL-35 antagonist.
  
  
  CONCLUSIONS
  IL-27 and IL-35 antagonists may be suitable goals for the treatment of chronic joint inflammation while their anti-inflammatory effects are not exerted via the changes in JBF.
authors.affiliation: Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Nasrin
authors.initials: N
authors.lastname: Houshmandi
authors.affiliation: Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences and Department of Physiology, Kerman University of Medical Sciences, Kerman, Iran. Electronic address: najafipourh@yahoo.co.uk.
authors.forename: Hamid
authors.initials: H
authors.lastname: Najafipour
authors.affiliation: Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences and Department of Physiology, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Siyavash
authors.initials: S
authors.lastname: Joukar
authors.affiliation: Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences and Department of Pathology, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Shahriar
authors.initials: S
authors.lastname: Dabiri
authors.affiliation: Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Abbasloo
authors.affiliation: Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Abdi
authors.affiliation: Gastroenterology and Hepathology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Safi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D002908:Chronic Disease; D005620:Freund's Adjuvant; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053765:Interleukin-12 Subunit p35 / Q000037:antagonists & inhibitors / Q000378:metabolism; D064094:Interleukin-27 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007719:Knee Joint / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; C506768:EBI3 protein, rat; D053765:Interleukin-12 Subunit p35; D064094:Interleukin-27; D007378:Interleukins; D015778:Minor Histocompatibility Antigens; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D021122:Protein Subunits; D007334:Insulin-Like Growth Factor I; D005620:Freund's Adjuvant
keywords: Chronic joint inflammation; Histopathology; IGF-1; IL-27; IL-35; Synovial blood flow