Interleukin-12 expression in human lymphomas and nonneoplastic lymphoid
disorders
J Schwaller, A Tobler, G Niklaus, N Hurwitz, I Hennig, MF Fey and B Borisch
Laboratory for Clinical and Experimental Research, Berne, Switzerland.
Interleukin-12 (IL-12), a cytokine with in vitro and in vivo
immunomodulatory effects, is produced by lymphocytes and stimulated
monocytes. Little is known about the production and possible role of IL- 12
in human lymphoproliferative disorders. We examined IL-12 expression by
immunohistochemistry using antibodies recognizing the p40, p35 subunits,
and the p70 heterodimeric IL-12 protein, and by Northern blot in lymph
nodes from patients with Hodgkin's disease (HD), non-Hodgkin's lymphomas
(NHL), and nonneoplastic lymphoid lesions. In the majority of the HD cases
(28 of 34), IL-12 immunoreaction was found in small lymphoid cells cultured
around Hodgkin and Reed-Sternberg (H&RS) cells. No IL-12 signal was
seen in H&RS cells. Transcripts for IL-12 were found by Northern and
dot blot analysis in 13 of 19 (IL-12 p40) and 11 of 19 (IL-12 p35) cases.
The HD cases were further examined for the presence of Epstein-Barr virus
(EBV) latent membrane protein (LMP-1). All cases with EBV-LMP-1 positivity
(22 of 34 cases) also expressed IL- 12. No IL-12 immunoreaction was found
in neoplastic cells of 33 cases of various NHLs, which were all LMP-1
negative and showed no EBV-genome sequence, as assessed by polymerase chain
reaction (PCR). In 24 nonneoplastic lymphoid lesions, few dispersed IL-12
positive cells were seen in the parafollicular area and in the sinus of the
lymph node. The marked presence of IL-12 in the majority of HD cases
indicates that IL- 12 might play a role in the pathobiology of HD,
suggesting that this cytokine is involved in EBV-positive HD.
Volume 85,
Issue 8,
pp. 2182-2188,
04/15/1995
Copyright © 1995 by The American Society of Hematology