Investigators and Projects
Up to 30% of patients with inflammatory diseases do not respond to moderate doses of steroids, resulting in inadequate disease control, continued inflammatory tissue damage and prolonged drug exposure (increasing the risk of steroid associated side-effects such as osteoporosis, hypertension, weight gain and diabetes mellitus).
Development of an assay to predict response to steroids and other immunosuppressive therapies would be a significant advance, enabling the clinical management of patients with a range of steroid-treated pathologies to be tailored to the individual, optimising their care and potentially improving therapeutic outcomes.
Our studies have revealed a subpopulation of CD4+ T-lymphocytes which are resistant to the anti-proliferative effects of steroids, and this has led us to propose a model of steroid resistant disease based on the selection of these steroid resistant (SR) cells. The principal focus of this project is inflammatory eye disease (uveitis). Most of the work is carried out with primary human cells that is peripheral blood mononuclear cells (PBMCs) that are cultured under various conditions and tested for the expression of cell surface markers using flow cytometry.
Steroid resistance is an important clinical component of many other diseases such as ulerative colitis and autoimmune hepatitis. This work is likely to have general relevance in these conditions too.
Schewitz-Bowers, L. P., Lee, R. W. J. and Dick A.D. (2010) Immune mechanisms of
Expert Review of Ophthalmology 5: 43-58
Lee, R. W. J., Schewitz, L. P., Nicholson, L. B., Dayan, C. M., and Dick, A. D. (2009) Steroid Refractory CD4+ T Cells in Patients with Sight-Threatening Uveitis, Invest.Ophthalmol.Vis.Sci. 50 4273-4278
Schewitz, L.P. Lee, R.W. Dayan, C.M. and Dick, A. D. (2009) Glucocorticoids and the emerging importance of T cell subsets in steroid refractory diseases Immunopharmacology & Immunotoxicology 31 1-22
Lee,R.W.J., T.J.Creed, L.P.Schewitz, P.V.Newcomb, L.B.Nicholson, A.D.Dick, and C.M.Dayan. (2007). CD4+CD25int T Cells in Inflammatory Diseases Refractory to Treatment with Glucocorticoids. J. Immunol. 179, 7941-7948.