Skip to main content
  • Poster presentation
  • Open access
  • Published:

Chronic anti-inflammatory treatment fails to prevent CNS disease in lupus-prone mice


Spontaneous development of systemic inflammation and autoimmunity results in brain atrophy and behavioral dysfunction in lupus-prone MRL-lpr mice. Based on beneficial effects of non-steroidal anti-inflammatory drugs in other CNS inflammation models, we test the hypothesis that chronic treatment with ibuprofen (COX-1/COX-2 inhibitor) attenuates behavioral deficits and neuronal loss in this model of neuropsychiatric lupus.

Materials and methods

To avoid confounding effects of repeated injections on performance in behavioral tasks, ibuprofen was provided in rodent chow from 5–19 weeks of age and an established behavioral battery was concurrently applied. Neuropathological and immunological parameters were estimated upon sacrifice using F4/80, CD3, and Fluoro Jade B (FJB) staining techniques. Transmission electron microscopy (EM) was also employed to the examine ultrastructural features of neurodegeneration in murine brains.


The density of F4/80-positive microglial cells was increased in brains of MRL-lpr mice fed with the control diet, but the treatment with ibuprofen neither prevented this activation nor normalized their behavioral performance. Similarly, no attenuation in infiltration of CD3-positive lymphocytes into the choroid plexus or density of dying (FJB-positive) neurons were seen. Paradoxically, ibuprofen increased serum levels of TNF-alpha and circulating immune complexes in both MRL-lpr and the less symptomatic MRL +/+ substrain. However, it did not promote lymphocyte infiltration into the brain or neurodegeneration in MRL +/+ control mice. EM revealed numerous dark neurons in MRL-lpr brains, but no evidence of blebbing of the nucleus or apoptotic bodies was found.


Taken together, present results suggest that activation of COX-dependent inflammatory pathways is not critical in the etiology of CNS dysfunction in MRL-lpr mice. Furthermore, modest amplification in systemic TNF-alpha levels do not seem to compromise the permeability of the blood-brain barrier, a condition proposed to be instrumental for CNS degeneration and behavioral dysfunction during lupus-like disease. Contrary to our expectation, nonapoptotic mechanisms appear to predominate the neuronal death in lupus mice.


  1. Lim GP, Yang F, Chu T, Chen P, Beech W, Teter B, Tran T, Ubeda O, Ashe KH, Frautschy SA, Cole GM: Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease. J Neurosci. 2000, 20: 5709-5714.

    CAS  PubMed  Google Scholar 

  2. Sakic B, Szechtman H, Denburg JA, Gorny G, Kolb B, Whishaw IQ: Progressive atrophy of pyramidal neuron dendrites in autoimmune MRL-lpr mice. J Neuroimmunol. 1998, 87: 162-170. 10.1016/S0165-5728(98)00085-X.

    Article  CAS  PubMed  Google Scholar 

  3. Sakic B, Szechtman H, Denburg JA: Neurobehavioral alteration in autoimmune mice. Neurosci Biobehav Rev. 1997, 21: 327-340. 10.1016/S0149-7634(96)00018-8.

    Article  CAS  PubMed  Google Scholar 

  4. Ballok DA, Woulfe J, Sur M, Cyr M, Sakic B: Hippocampal damage in mouse and human forms of systemic autoimmune disease. Hippocampus. 2004, 14: 649-661. 10.1002/hipo.10205.

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and permissions

About this article

Cite this article

Ballok, D., Sakic, B. Chronic anti-inflammatory treatment fails to prevent CNS disease in lupus-prone mice. Ann Gen Psychiatry 5 (Suppl 1), S212 (2006).

Download citation

  • Published:

  • DOI: