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Patterns of cytokine gene expression in infectious mononucleosis
HD Foss, H Herbst, M Hummel, I Araujo, U Latza, C Rancso, F Dallenbach and H Stein
Institute of Pathology, Klinikum Steglitz, Free University of Berlin,
Germany.
Primary infection with Epstein-Barr virus (EBV) may arise as infectious
mononucleosis (IM) in adolescents and young adults. Morphologically, IM-
affected lymphoid tissue is characterized by expanded interfollicular areas
with formation of atypical lymphoid blasts. It is assumed that morphology
and clinical presentation of IM are related to characteristic patterns of
cytokine production by EBV-infected and reactive cells. We studied IM
tonsils of eight patients and six normal tonsils with a double in situ
hybridization procedure using [35S]- labeled RNA probes specific for
various cytokines and digoxigenin- labeled probes for the detection of the
nuclear EBV encoded RNA transcripts, EBER 1 and 2. All of the IM cases
displayed the same distinct cytokine gene expression pattern. When compared
with interfollicular areas of normal tonsils, expression of lymphotoxin
(LT), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and
IL-1 beta, but not IL-8 or IL-1 alpha was strongly enhanced in
interfollicular areas in IM tonsils. LT was expressed predominantly by
EBV-infected cells. TNF-alpha transcripts were also present in EBV-
infected cells, although in smaller proportions. IL-6 specific signals were
only found in few EBV-infected cells. IL-1 alpha-, IL-1 beta-, and
IL-8-specific signals were not observed in EBV-infected cells, but were
present at high signal intensity in many cells within and around foci of
EBV-infected cells (IL-1 beta), next to areas of necrosis (IL-8, IL- 1
beta), or in epithelial cells (IL-1 alpha). These data suggest that EBV
infection in form of IM results in induction of specific sets of cytokine
genes in EBV-infected and in neighboring EBV-negative cells contributing to
the characteristic morphology and cellular arrangement of the lesion as
well as the clinical presentation.
Volume 83,
Issue 3,
pp. 707-712,
02/01/1994
Copyright © 1994 by The American Society of Hematology
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