K/B×N serum transfer arthritis is delayed and less severe in leukaemia inhibitory factor (LIF)-deficient mice

Authors

  • A. Upadhyay,

    1. Department of Pharmaceutical Biology, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville
    Search for more papers by this author
  • D. Senyschyn,

    1. Department of Pharmaceutical Biology, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville
    Search for more papers by this author
  • L. Santos,

    1. Centre for Inflammatory Diseases, Monash Medical Centre, Clayton, Vic.
    2. School of Veterinary Medicine, University College Dublin, Dublin, Republic of Ireland
    Search for more papers by this author
  • R. Gu,

    1. Centre for Inflammatory Diseases, Monash Medical Centre, Clayton, Vic.
    Search for more papers by this author
  • G. J Carroll,

    1. Department of Rheumatology, Fremantle Hospital
    2. School of Medicine, University of Notre Dame Australia (Fremantle), Fremantle
    3. School of Medicine and Pharmacology, University of Western Australia, Perth, WA
    Search for more papers by this author
  • J. A. Jazayeri

    Corresponding author
    1. Department of Pharmaceutical Biology, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville
    2. School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW, Australia
      J. A. Jazayeri, School of Biomedical Sciences, Charles Sturt University, Boorooma Street, PO Box 588, Wagga Wagga, NSW 2678, Australia. E-mail: jjazayeri@csu.edu.au
    Search for more papers by this author

J. A. Jazayeri, School of Biomedical Sciences, Charles Sturt University, Boorooma Street, PO Box 588, Wagga Wagga, NSW 2678, Australia. E-mail: jjazayeri@csu.edu.au

Summary

This study is investigating the role of leukaemia inhibitory factor (LIF) in the development of inflammation and joint damage in the mouse K/B×N serum transfer arthritis model. LIF knock-out (LIF−/−) mice were generated by mating heterozygote females (LIF+/−) with heterozygote males. Arthritis was induced in 8–20-week-old LIF knock-out mice (LIF−/−) by intraperitoneal injection of pooled K/B×N sera (50 µl) on days 0 and 2. Clinical disease was scored daily for 6 days. Safranin-O and haematoxylin-stained sections were scored for synovitis, joint space exudate, cartilage degradation and bone damage. RNA was extracted from ankle joints and used to investigate gene expression levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1, LIF, LIF receptor, oncostatin M (OSM), OSM receptor, IL-6 and their common receptor subunit gp130 by quantitative reverse transcription–polymerase chain reaction (qRT–PCR). The results show that wild-type mice developed severe clinically overt polyarthritis. In contrast, LIF−/− mice showed a more than 50% reduction in clinical arthritis severity. Significantly lower histological scores were observed in LIF−/− mice compared to wild-type disease controls. LIF−/− mice had histopathological scores that were similar to normal healthy mice. IL-6 subfamily cytokine and receptor subunit expression remained unchanged. The expression levels for IL-6 were reduced significantly in all the diseased mice, whether wild-type or LIF−/− mice (P < 0·001), compared to healthy wild-type mice. We conclude that LIF contributes to the development of disease in the K/B×N serum transfer model of arthritis. These results provide further evidence for the role of LIF in inflammation and cartilage bone resorption and provide impetus to test the effects of LIF blockade as a therapeutic strategy in rheumatoid arthritis.

Ancillary