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Interleukin-6 gene expression in Castleman's disease
MB Leger-Ravet, M Peuchmaur, O Devergne, J Audouin, M Raphael, J Van Damme, P Galanaud, J Diebold and D Emilie
INSERM U131, Clamart, France.
Defined by histological criteria, Castleman's disease (CD) is a clinically
and histologically heterogeneous syndrome. The functional status of immune
cells in affected tissues may vary between the different forms of the
disease. To address this question, the expression of cytokine genes in
eight CD lymph nodes was analyzed by in situ hybridization. Two lymph nodes
were taken from patients with a localized form of the disease associated
with systemic manifestations, two from patients with a localized form
without systemic symptoms, and four from patients with a multicentric form.
Five lymph nodes exhibiting a benign follicular hyperplasia were used as
controls. The interleukin-6 (IL-6) gene was expressed at a very high level
in two cases: the two localized forms of CD associated with systemic
manifestations. IL-6 gene overexpression occurred inside follicles of these
lymph nodes. The morphology of follicular cells hybridizing with the IL-6
probe or labeled with an anti-IL-6 monoclonal antibody suggested that
follicular dendritic cells expressed the IL-6 gene. In contrast, no IL-6
gene expression was detected inside follicles of the six other CD lymph
nodes or of the five control lymph nodes. In interfollicular areas, IL-6
gene-expressing cells were detected in all lymph nodes by both in situ
hybridization and immunohistochemistry. In CD lymph nodes, positive cells
were located outside sinuses, in close contact with blood vessels and
plasma cells. This distribution was clearly different from that observed in
control lymph nodes, in which IL-6 gene-expressing cells were present
inside sinuses. A similar difference between CD and control lymph nodes was
observed for the distribution of IL-1 beta and IL-1 alpha gene-expressing
cells in interfollicular areas. The morphology of interfollicular
IL-6-producing cells was heterogeneous, consistent with that of
macrophages, interdigitating cells, lymphocytes, and endothelial cells, and
different from that of plasma cells. Taken together these results show that
CD is consistently associated with a particular pattern of IL-6 gene
expression in interfollicular areas whereas elevated IL-6 gene expression
inside follicles only occurs in the localized form of the disease
associated with systemic manifestations. The variable pattern of IL-6 gene
expression as well as the clinical and histologic heterogeneity of CD
indicate that different immune mechanisms may be involved in the different
forms of this disease.
Volume 78,
Issue 11,
pp. 2923-2930,
12/01/1991
Copyright © 1991 by The American Society of Hematology

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