Anti-tumor necrosis factor α treatment of interferon-α-induced murine lupus nephritis reduces the renal macrophage response but does not alter glomerular immune complex formation

Ramalingam Bethunaickan, Ranjit Sahu, Zheng Liu, Yi Ting Tang, Weiqing Huang, Osarieman Edegbe, Haiou Tao, Meera Ramanujam, Michael P. Madaio, Anne Davidson

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Objective. To analyze the mechanism for the therapeutic effects of tumor necrosis factor α (TNFα) inhibition in a murine model of systemic lupus erythematosus. Methods. We used the (NZB × NZW)F1 (NZB/ NZW) mouse model of interferon-α-induced lupus nephritis and treated mice with TNF receptor type II (TNFRII) Ig after TNFα expression was detected in the kidneys. Autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA), and autoantibodyforming cells were determined using an enzyme-linked immunospot assay. Activation of splenocytes was analyzed by flow cytometry. Kidneys were harvested and analyzed using flow cytometry, immunohistochemistry, ELISA, Western blotting, and real-time polymerase chain reaction. Results. TNFRII Ig treatment stabilized nephritis and markedly prolonged survival. Autoantibody production and systemic immune activation were not inhibited, but the renal response to glomerular immune complex deposition was attenuated. This was associated with decreases in renal production of chemokines, renal endothelial cell activation, interstitial F4/80high macrophage accumulation, tubular damage, and oxidative stress. In contrast, perivascular lymphoid aggregates containing B cells, T cells, and dendritic cells accumulated unabated. Conclusion. Our data suggest that TNFα is a critical cytokine that amplifies the response of the nephron to immune complex deposition, but that it has less influence on the response of the systemic vasculature to inflammation.

Original languageEnglish (US)
Pages (from-to)3399-3408
Number of pages10
JournalArthritis and Rheumatism
Volume64
Issue number10
DOIs
StatePublished - Oct 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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