Lymphotoxin, tumour necrosis factor and interleukin‐6 gene transcripts are present in Hodgkin and Reed‐Sternberg cells of most Hodgkin's disease cases

Abstract

Tissue specimens from 26 cases of Hodgkin's disease (HD) and six HD-derived cell lines were analysed for tumour necrosis factor (TNF), lymphotoxin (LT), and interleukin (IL)-6 RNA transcripts by in situ hybridization, in some cases subsequent to immunohistology for CD30 antigen. LT and TNF transcripts were found in tumour cells of all cases; IL-6 gene transcripts were detectable in 19/23 cases. Presence of RNA specific for these cytokines was not correlated with any of the following parameters: sex, symptoms and histotype, as well as immunophenotype and association of the tumour cells with Epstein-Barr virus. Rather, the presence of LT, TNF and IL-6 transcripts appeared to characterize Hodgkin and Reed-Sternberg cells in general, supporting concepts which suggest that HD represents a malignancy of cytokine secreting activated cells, and that many of the features distinguishing HD from other malignant lymphomas may ultimately be due to expression of cytokines. LT and TNF RNA transcripts were also found in five HD-derived cell lines, whereas supernatants of these cell lines contained high levels of LT, but low or undetectable levels of TNF activity. This suggests that, although not detectable at the level of RNA transcripts, differences between HD cases may exist on the level of cytokine gene transcript processing, translation and polypeptide secretion.

Molecular mechanisms of constitutive NF-κB/Rel activation in Hodgkin/Reed-Sternberg cells

“…Reh (lanes 1 ± 4), HDLM-2 (lanes 5 ± 8), L1236 (lanes 9 ± 12), KMH-2 (lanes 13 ± 16) or L428 cells (lanes 17 ± 19) were incubated for 0 to 8 h with the proteasomal inhibitor ALLN (50 mg/ml). (Hsu et al, 1989;Xerri et al, 1992;Foss et al, 1993;Wolf et al, 1996;Serano et al, 1997). Some of these cytokines are potential activators of NF-kB or are regulated by NF-kB on the transcriptional level.…”

Interleukin‐6 and its receptor in cancer

“…Moreover, IL-6 messenger RNA (mRNA) is expressed by Reed-Sternberg cells in approximately 80% of patients examined. 78 Proliferation of certain B-cell-and T-cell-derived human lymphoma cell lines from non-Hodgkin lymphomas can be stimulated by autocrine-produced IL-6.…”

Down-regulation of BOB.1/OBF.1 and Oct2 in classical Hodgkin disease but not in lymphocyte predominant Hodgkin disease correlates with immunoglobulin transcription

“…4,15 The Oct2 probe was prepared from complementary DNA (cDNA) that had been amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) from a B-cell line and cloned into the appropriate plasmids. After linearization of the plasmids with restriction enzymes, anti-sense and sense (control) transcripts were generated, using T7 or SP6 RNA-polymerase with the incorporation of [ 35 S]-dUTP.…”