Inactivation of the IL-6 gene prevents development of multicentric Castleman's disease in C/EBP beta-deficient mice

doi:10.1084/jem.184.4.1561

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Inactivation of the IL-6 gene prevents development of multicentric Castleman's disease in C/EBP beta-deficient mice

I Screpanti, P Musiani, D Bellavia, M Cappelletti, FB Aiello, M Maroder, L Frati, A Modesti, A Gulino and V Poli
Dipartimento di Medicino Sperimentale c Patologia, Universita La Sapienza, Roma, Italy.

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.
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