A role for parathyroid hormone-related protein in the pathogenesis of inflammatory/autoimmune diseases

Our increased understanding of the critical role of cytokines in chronic in flammatory/autoimmune diseases has led to the recent development of effecti ve anti-cytokine treatments. In particular, agents blocking the function of TNF-alpha, a cytokine first identified as an endotoxin-inducible mediator of tumor cell necrosis, are now licensed for the treatment of rheumatoid ar thritis (RA) and inflammatory bowel disease. However, TNF-alpha is but one member of a cytokine network that is responsible for mediating these inflam matory disorders. Therefore, as our understanding of the pathophysiologic r ole of other members of this inflammatory network increases, other cytokine s may similarly be identified as effective targets for treatment. In this a rticle, we will review evidence which suggests that parathyroid hormone-rel ated protein (PTHrP), a peptide which, like TNF-alpha, was first identified because of its effects in the setting of malignancy, may in fact serve an important non-neoplastic, physiologic function by mediating the inflammator y/autoimmune host response. Data identifying PTHrP as a member of the cytok ine network induced in multi-organ inflammation and rheumatoid arthritis wi ll be summarized, initial evidence comparing the therapeutic efficacy of PT HrP- vs. TNF-alpha -blockade in the treatment of endotoxemia will be review ed, and potential future areas of research, including assessment of the eff ects of PTHrP blockade in the treatment of RA, will be discussed. (C) 2001 Elsevier Science B.V. All rights reserved.