title: Inactivation of the IL-6 gene prevents development of multicentric Castleman's disease in C/EBP beta-deficient mice.
abstract: Castleman's disease is a lymphoproliferative disorder thought to be related to deregulated production of IL-6. We have previously shown that mice lacking the trans-acting factor C/EBP beta, a transcriptional regulator of IL-6 and a mediator of IL-6 intracellular signaling, develop a pathology nearly identical to multicentric Castleman's disease, together with increasingly high levels of circulating IL-6. We describe here how the simultaneous inactivation of both IL-6 and C/EBP beta genes prevents the development of pathological traits of Castleman's disease observed in C/EBP beta-deficient mice. Histological and phenotypic analysis of lymph nodes and spleen of double mutant mice did not show either the lymphoadenopathy and splenomegaly or the abnormal expansion of myeloid, B and plasma cell compartments observed in C/EBP beta-/- mice, while B cell development, although delayed, was normal. Our data demonstrate that IL-6 is essential for the development of multicentric Castleman's disease in C/EBP beta-/- mice.
authors.affiliation: Dipartimento di Medicino Sperimentale c Patologia, Università La Sapienza, Roma, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Screpanti
authors.forename: P
authors.initials: P
authors.lastname: Musiani
authors.forename: D
authors.initials: D
authors.lastname: Bellavia
authors.forename: M
authors.initials: M
authors.lastname: Cappelletti
authors.forename: F B
authors.initials: FB
authors.lastname: Aiello
authors.forename: M
authors.initials: M
authors.lastname: Maroder
authors.forename: L
authors.initials: L
authors.lastname: Frati
authors.forename: A
authors.initials: A
authors.lastname: Modesti
authors.forename: A
authors.initials: A
authors.lastname: Gulino
authors.forename: V
authors.initials: V
authors.lastname: Poli
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D022762:CCAAT-Enhancer-Binding Proteins; D005871:Castleman Disease / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005434:Flow Cytometry; D015850:Interleukin-6 / Q000235:genetics*; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D010950:Plasma Cells / Q000473:pathology; D013154:Spleen / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins