title: TNFalpha inhibition in MRL/lpr mice ameliorates pulmonary but not renal disease.
abstract: TNFalpha inhibition has a clearly beneficial effect in a number of arthritides and in Crohn's disease. The exact mechanism of action is uncertain with studies showing inhibition of chemokines, inhibition of adhesion molecule expression, and improved T-cell function. Unlike most therapeutic interventions for autoimmune disease, TNFalpha inhibition appears to act on specific pathologic processes. It is not known how wide-spread these TNFalpha-mediated pathologic processes are. Efforts to expand the use of TNFalpha inhibition have had notable successes but have been disappointing in other disorders. We hypothesized that TNFalpha-mediated pathologic processes might play a significant role in the end-organ effects seen in SLE. We modeled SLE by using MRL/lpr mice and treated with two types of TNFalpha inhibitor. Pulmonary disease was significantly improved in the treated groups compared to controls. In contrast, renal disease was unaffected suggesting that in lupus, where multiple organs are affected, different pathologic processes may be mediating the end-organ damage. This has important implications for designing therapeutics for SLE.
authors.affiliation: Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Nahmah
authors.initials: N
authors.lastname: Kim
authors.forename: Lashon
authors.initials: L
authors.lastname: Ussin
authors.forename: Xin
authors.initials: X
authors.lastname: Cheng
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Murali
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Sullivan
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D004247:DNA / Q000276:immunology; D005260:Female; D007674:Kidney Diseases / Q000378:metabolism*; D008171:Lung Diseases / Q000378:metabolism*; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D013154:Spleen / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha; D004247:DNA