| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Activity Suppresses Activation of Infiltrating Macrophages in Experimental Autoimmune Uveoretinitis
1From the Department of Ophthalmology, University of Aberdeen, Aberdeen, Scotland, United Kingdom; and the 2Division of Ophthalmology, University of Bristol, Bristol, United Kingdom.
PURPOSE. During experimental autoimmune uveoretinitis (EAU), infiltrating macrophages become activated to express nitric oxide synthase (NOS)-2 and generate nitric oxide (NO). The current study was designed to determine whether neutralizing TNF activity with a soluble fusion protein of TNFp55 receptor (sTNFr-IgG) inhibits macrophage activation, thereby contributing to reduced tissue damage observed with such treatment.
METHODS. EAU was induced in Lewis rats by active immunization with soluble retinal extract (RE) and pertussis toxin (intraperitoneally), and animals were treated on days 6 and 8 after immunization with either sTNFr-IgG or human (hu)IgG. Disease course and severity were noted clinically, and eyes were enucleated for histologic scoring, including TUNEL immunofluorescence, at various stages of disease. Infiltrating retinal macrophages were isolated through a density gradient and subsequently phenotyped by flow cytometry, analyzed for ability to produce nitrite, either spontaneously or after cytokine stimulation, and assayed by PCR for cytokine gene expression.
RESULTS. Neutralizing TNF activity suppressed tissue damage without impeding myeloid cell infiltrate. Moreover, with sTNFr-IgG treatment, infiltrating macrophages demonstrated reduced nitrite production at the height of disease, and the level of apoptosis within the retina of both ED1+ cells and resident cells was reduced. PCR analysis demonstrated a significant increase in TGFß signal and absent or low TNF signal throughout the disease course after treatment with sTNFr-IgG.
CONCLUSIONS. sTNFr-IgG successfully suppresses retinal damage and impairs macrophage activation but not trafficking during EAU. sTNFr-IgG–mediated suppression of NO production results in reduced levels of apoptosis of inflammatory cells and reduction in photoreceptor damage.
This article has been cited by other articles:
|
|
 |
|
  M. A. Fields, M. Zheng, P. Wall, S. Oberg, and S. S. Atherton Uniocular Anterior Chamber Inoculation of a Tumor Necrosis Factor Alpha-Expressing Recombinant of Herpes Simplex Virus Type 1 Results in More Rapid Destruction and Increased Viral Replication in the Retina of the Uninoculated Eye J. Virol., May 15, 2008; 82(10): 5068 - 5078. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Talmadge Pathways Mediating the Expansion and Immunosuppressive Activity of Myeloid-Derived Suppressor Cells and Their Relevance to Cancer Therapy Clin. Cancer Res., September 15, 2007; 13(18): 5243 - 5248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Adriaansen, M Khoury, C J de Cortie, F J Fallaux, P Bigey, D Scherman, D J Gould, Y Chernajovsky, F Apparailly, C Jorgensen, et al. Reduction of arthritis following intra-articular administration of an adeno-associated virus serotype 5 expressing a disease-inducible TNF-blocking agent Ann Rheum Dis, September 1, 2007; 66(9): 1143 - 1150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Biester, C. Deuter, H. Michels, R. Haefner, J. Kuemmerle-Deschner, D. Doycheva, and M. Zierhut Adalimumab in the therapy of uveitis in childhood Br. J. Ophthalmol., March 1, 2007; 91(3): 319 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kitamei, K. Iwabuchi, K. Namba, K. Yoshida, Y. Yanagawa, N. Kitaichi, M. Kitamura, S. Ohno, and K. Onoe Amelioration of experimental autoimmune uveoretinitis (EAU) with an inhibitor of nuclear factor-{kappa}B (NF-{kappa}B), pyrrolidine dithiocarbamate J. Leukoc. Biol., June 1, 2006; 79(6): 1193 - 1201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Calder, L. B. Nicholson, and A. D. Dick A Selective Role for the TNF p55 Receptor in Autocrine Signaling following IFN-{gamma} Stimulation in Experimental Autoimmune Uveoretinitis J. Immunol., November 15, 2005; 175(10): 6286 - 6293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Barcelos, A. Talvani, A. S. Teixeira, L. Q. Vieira, G. D. Cassali, S. P. Andrade, and M. M. Teixeira Impaired inflammatory angiogenesis, but not leukocyte influx, in mice lacking TNFR1 J. Leukoc. Biol., August 1, 2005; 78(2): 352 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E W Lindstedt, G S Baarsma, R W A M Kuijpers, and P M van Hagen Anti-TNF-{alpha} therapy for sight threatening uveitis Br. J. Ophthalmol., May 1, 2005; 89(5): 533 - 536. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Murphy, K. Greiner, J. Plskova, L. Duncan, A. Frost, J. D. Isaacs, P. Rebello, H. Waldmann, G. Hale, J. V. Forrester, et al. Neutralizing Tumor Necrosis Factor Activity Leads to Remission in Patients With Refractory Noninfectious Posterior Uveitis Arch Ophthalmol, June 1, 2004; 122(6): 845 - 851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Greiner, C. C. Murphy, F. Willermain, L. Duncan, J. Plskova, G. Hale, J. D. Isaacs, J. V. Forrester, and A. D. Dick Anti-TNF{alpha} Therapy Modulates the Phenotype of Peripheral Blood CD4+ T Cells in Patients with Posterior Segment Intraocular Inflammation Invest. Ophthalmol. Vis. Sci., January 1, 2004; 45(1): 170 - 176. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
