UMMS Affiliation

Department of Medicine, Division of Rheumatology

Publication Date


Document Type



Animals; *Antibodies; Antigens, CD; Arthritis, Experimental; Cytokines; Disease Models, Animal; Genetic Predisposition to Disease; Immunization, Passive; Inflammation; Interleukin-1; Interleukin-6; Mice; Mice, Transgenic; Receptors, Interleukin-1; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Tarsus, Animal; Tumor Necrosis Factor-alpha


Immunopathology | Musculoskeletal Diseases | Rheumatology | Skin and Connective Tissue Diseases


In spontaneous inflammatory arthritis of K/BxN T cell receptor transgenic mice, the effector phase of the disease is provoked by binding of immunoglobulins (Igs) to joint surfaces. Inflammatory cytokines are known to be involved in human inflammatory arthritis, in particular rheumatoid arthritis, although, overall, the pathogenetic mechanisms of the human affliction remain unclear. To explore the analogy between the K/BxN model and human patients, we assessed the role and relative importance of inflammatory cytokines in K/BxN joint inflammation by transferring arthritogenic serum into a panel of genetically deficient recipients. Interleukin (IL)-1 proved absolutely necessary. Tumor necrosis factor (TNF)-alpha was also required, although seemingly less critically than IL-1, because a proportion of TNF-alpha-deficient mice developed robust disease. There was no evidence for an important role for IL-6. Bone destruction and reconstruction were also examined. We found that all mice with strong inflammation exhibited the bone erosion and reconstruction phenomena typical of K/BxN arthritis, with no evidence of any particular requirement for TNFalpha for bone destruction. The variability in the requirement for TNF-alpha, reminiscent of that observed in treated rheumatoid arthritis patients, did not appear genetically programmed but related instead to subtle environmental changes.

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DOI of Published Version



J Exp Med. 2002 Jul 1;196(1):77-85. doi: 10.1084/jem.20020439

Journal/Book/Conference Title

The Journal of experimental medicine


At the time of publication, Ellen Gravallese was not yet affiliated with the University of Massachusetts Medical School.

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This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.