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Cytokine and Chemokine mRNA Produced in
Synovial Tissue Chronically Infected with
Chlamydia trachomatis and C. pneumoniae
HERVE C. GERARD, ZHAO WANG, JUDITH A. WHITTUM-HUDSON, HANI El-GABALAWY, RAFAELA GOLDBACH-MANSKY, THOMAS BARDIN, H. RALPH SCHUMACHER, and ALAN P. HUDSON
ABSTRACT.
Methods. RNA/cDNA was prepared from synovial biopsies of 4 patients with chronic arthritis and joint infection with C. trachomatis, 6 with C. pneumoniae at that site, 3 uninfected healthy controls, and 3 patients with undifferentiated oligoarthritis (UO) who were PCR negative for all organisms assayed. Real-time RT-PCR was used to assess relative mRNA levels from 12 cytokine and 2 chemokine genes (IL-1a, IL-1ß, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, IFN-g, TNF-a, MCP-1, RANTES). Input loading was normalized to 18S rRNA. Data were obtained for each mRNA from each sample in triplicate in comparison to the same mRNA level in the controls. Results. In most C. trachomatis infected synovial tissue samples, high levels of IL-10 mRNA were present, with less mRNA for IL-8, IL-15, IFN-g, and TNF-a. Synovial tissues from chronic arthritis patients with synovial C. pneumoniae showed significant levels of mRNA solely for IL-8 and IL-1ß. All other cytokine messengers assessed in each sample from each patient group were at or near control level. One patient with C. pneumoniae showed a high transcript level for RANTES, and one patient with C. trachomatis showed a high transcript level for MCP-1. No patient with UO showed elevated messenger level for any cytokines assayed, but RANTES mRNA was elevated in each. Conclusion. Our data suggest that while both C. trachomatis and C. pneumoniae have been associated with inflammatory joint disease, each elicits a somewhat different steady-state profile of mRNA encoding relevant cytokines and chemokines during chronic infection of synovial tissue. Precisely how these differing profiles relate to clinical aspects of synovial inflammation will require further study, but the observations confirm and extend data indicating potentially important differences in the pathobiology of these 2 bacterial species. (J Rheumatol 2002;29:1827-35) Key Indexing Terms:
CYTOKINES
From the Departments of Immunology and Microbiology, Internal Medicine, and Ophthalmology, Wayne State University School of Medicine, and the Department of Veterans Affairs (DVA) Medical Center, Detroit, Michigan; the Arthritis and Rheumatism Branch, NIAMS, National Institutes of Health, Bethesda, Maryland, USA; the Fédération de Rhumatologie, Hôpital Lariboisière, Paris, France; and the Division of Rheumatology, Department of Medicine, University of Pennsylvania School of Medicine, and the DVA Medical Center, Philadelphia, Pennsylvania, USA. Supported by NIH grants AR-42541 and AI-44055 (APH), AI-44493 (JAW-H), and AR-47186 (HCG), and grants from the DVA Medical Research Service (APH, HRS). H.C. Gérard, PhD, Research Scientist; Z. Wang, MS, Research Associate; A.P. Hudson, PhD, Professor of Microbiology, Department of Immunology and Microbiology; J.A. Whittum-Hudson, PhD, Professor of Internal Medicine, Immunology, and Ophthalmology, Departments of Internal Medicine, Ophthalmology, and Immunology and Microbiology, Wayne State University School of Medicine; H. El-Gabalawy, MD; R. Goldbach-Mansky, MD, Clinical Investigators, Arthritis and Rheumatism Branch, NIAMS, NIH; T. Bardin, MD, Professeur de Rhumatologie, Hôpital Lariboisière; H.R. Schumacher, MD, Professor of Medicine, University of Pennsylvania School of Medicine, and DVA Medical Center, Philadelphia. Address reprint requests to Dr. A.P. Hudson, Department of Immunology and Microbiology, Wayne State University School of Medicine, Gordon H. Scott Hall, 540 East Canfield Avenue, Detroit, MI 48201. E-mail: ahudson@med.wayne.edu Submitted May 30, 2001; revision accepted March 7, 2002. |