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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


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