The severity of experimental autoimmune cystitis can be ameliorated by Anti-CXCL10 Ab treatment

Udai P. Singh, Narendra P. Singh, Honbing Guan, Venkatesh L. Hegde, Robert L. Price, Dennis D. Taub, Manoj K. Mishra, Mitzi Nagarkatti, Prakash S. Nagarkatti

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background: Interstitial cystitis (IC), more recently called painful bladder syndrome (PBS) is a complex disease associated with chronic bladder inflammation that primarily affects women. Its symptoms include frequent urinary urgency accompanied by discomfort or pain in the bladder and lower abdomen. In the United States, eight million people, mostly women, have IC/PBS. New evidence that autoimmune mechanisms are important in the pathogenesis of IC/PBS triggered interest. Methodology/Principal Findings: SWXJ mice immunized with a homogenate of similar mice's urinary bladders develop an autoimmune phenotype comparable to clinical IC with functional and histological alterations confined to the urinary bladder. Using the murine model of experimental autoimmune cystitis (EAC), we found that serum levels of CXCR3 ligand and local T helper type 1 (Th1) cytokine are elevated. Also, IFN-γ-inducible protein10 (CXCL10) blockade attenuated overall cystitis severity scores; reversed the development of IC; decreased local production of CXCR3 and its ligands, IFN-γ, and tumor necrosis factor-α (TNF-α); and lowered systemic levels of CXCR3 ligands. Urinary bladder CD4+ T cells, mast cells, and neutrophils infiltrates were reduced following anti-CXCL10 antibody (Ab) treatment of mice. Anti-CXCL10 Ab treatment also reversed the upregulated level of CXCR3 ligand mRNA at urinary bladder sites. The decreased number and percentage of systemic CD4+ T cells in EAC mice returned to normal after anti-CXCL10 Ab treatment. Conclusion/Significance: Taken together, our findings provide important new information about the mechanisms underlying EAC pathogenesis, which has symptoms similar to those of IC/PBS. CXCL10 has the potential for use in developing new therapy for IC/PBS.

Original languageEnglish (US)
Article numbere79751
JournalPLoS ONE
Volume8
Issue number11
DOIs
StatePublished - Nov 21 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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