Functional Heterogeneity and Pathogenic Significance of Interleukin-6 in B-cell Lymphomas

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 1992 Oct 11

PMID 1415484

Citations 1

Authors

S M Hsu

S S Xie

J A Waldron Jr

Affiliations

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Abstract

A possible autocrine effect of interleukin-6 (IL-6) on the growth and differentiation of the tumor cells of 55 B-cell lymphomas was examined. Interleukin-6 was detected in a few types of B-cell lymphomas, including polymorphic immunocytoma (PI), small lymphocytic lymphoma (SLL), and immunoblastic lymphoma (IBL) with or without plasmacytoid differentiation. In PI and in IBL with plasmacytoid differentiation (IBL-P), IL-6 was detected only in immunoglobulin-containing plasmacytoid cells, and it was absent from most proliferating (Ki-67/PCNA-positive) lymphoma cells. In SLL, IL-6 was not observed in lymphoplasmacytoid cells; instead, IL-6 was observed in transformed (Ki-67/PCNA-positive) tumor cells in proliferation centers. The lymphoplasmacytoid cells in SLL exhibited a phenotype (IL-6/glutathione-S-transferase-pi [GST-pi]-negative), different from that of normal plasma cells (IL-6-negative/GST-pi-positive) and from the plasmacytoid cells (IL-6/GST-pi-positive) in PI and IBL-P. In IBL without obvious plasmacytoid differentiation, IL-6 was detected in most tumor cells that were highly proliferative (Ki-67/PCNA-positive). In this study, IL-6 was undetectable in most lymphomas related to follicular centers, in lymphoblastic lymphoma, in small noncleaved cell lymphomas of the Burkitt and non-Burkitt types, and in diffuse large cell lymphoma. This finding is compatible with a previous finding that IL-6 mRNA was absent from follicular center cells in reactive lymphoid tissues. The functions of IL-6 in these lymphomas may be quite diverse. It appears that IL-6, as an autocrine factor, is responsible for the plasmacytoid differentiation of lymphoma cells in IP and some IBL (IBL-P). The differentiation of lymphoplasmacytoid lymphoma cells in SLL, however, may not be mediated by an autocrine IL-6 mechanism. Interleukin-6 may provide a growth signal, rather than acting as a differentiation factor, for some IBL cells and for some transformed tumor cells in proliferation centers in SLL.

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References

Hsu S, Xie S, Hsu P, Waldron Jr J . Interleukin-6, but not interleukin-4, is expressed by Reed-Sternberg cells in Hodgkin's disease with or without histologic features of Castleman's disease. Am J Pathol. 1992; 141(1):129-38. PMC: 1886582. View

Hsu S, Soban E . Color modification of diaminobenzidine (DAB) precipitation by metallic ions and its application for double immunohistochemistry. J Histochem Cytochem. 1982; 30(10):1079-82. DOI: 10.1177/30.10.6182185. View

Wolvekamp M, Marquet R . Interleukin-6: historical background, genetics and biological significance. Immunol Lett. 1990; 24(1):1-9. DOI: 10.1016/0165-2478(90)90028-o. View

Espevik T, Waage A, Faxvaag A, Shalaby M . Regulation of interleukin-2 and interleukin-6 production from T-cells: involvement of interleukin-1 beta and transforming growth factor-beta. Cell Immunol. 1990; 126(1):47-56. DOI: 10.1016/0008-8749(90)90299-7. View

Elias J, Lentz V . IL-1 and tumor necrosis factor synergistically stimulate fibroblast IL-6 production and stabilize IL-6 messenger RNA. J Immunol. 1990; 145(1):161-6. View

Takatsuki F, Okano A, Suzuki C, Chieda R, Takahara Y, Hirano T . Human recombinant IL-6/B cell stimulatory factor 2 augments murine antigen-specific antibody responses in vitro and in vivo. J Immunol. 1988; 141(9):3072-7. View

Shalaby M, Waage A, Espevik T . Cytokine regulation of interleukin 6 production by human endothelial cells. Cell Immunol. 1989; 121(2):372-82. DOI: 10.1016/0008-8749(89)90036-1. View

Bosseloir A, Hooghe-Peters E, Heinen E, Cormann N, Vanhaelst L, Simar L . Localization of interleukin 6 mRNA in human tonsils by in situ hybridization. Eur J Immunol. 1989; 19(12):2379-81. DOI: 10.1002/eji.1830191230. View

Yoshizaki K, Matsuda T, Nishimoto N, Kuritani T, Taeho L, Aozasa K . Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman's disease. Blood. 1989; 74(4):1360-7. View

10.

Horii Y, Muraguchi A, Suematsu S, Matsuda T, Yoshizaki K, Hirano T . Regulation of BSF-2/IL-6 production by human mononuclear cells. Macrophage-dependent synthesis of BSF-2/IL-6 by T cells. J Immunol. 1988; 141(5):1529-35. View

11.

Tanaka Y, Saito K, Shirakawa F, Ota T, Suzuki H, Eto S . Production of B cell-stimulating factors by B cells in patients with systemic lupus erythematosus. J Immunol. 1988; 141(9):3043-9. View

12.

Hsu S . Phenotypic expression of cells of stationary elements in human lymphoid tissues. A histochemical and immunohistochemical study. Hematol Pathol. 1987; 1(1):45-56. View

13.

Waseem N, Lane D . Monoclonal antibody analysis of the proliferating cell nuclear antigen (PCNA). Structural conservation and the detection of a nucleolar form. J Cell Sci. 1990; 96 ( Pt 1):121-9. DOI: 10.1242/jcs.96.1.121. View

14.

Black K, Garrett I, Mundy G . Chinese hamster ovarian cells transfected with the murine interleukin-6 gene cause hypercalcemia as well as cachexia, leukocytosis and thrombocytosis in tumor-bearing nude mice. Endocrinology. 1991; 128(5):2657-9. DOI: 10.1210/endo-128-5-2657. View

15.

Bertolini J, Benson E . The role of human interleukin-6 in B-cell isotype regulation and differentiation. Cell Immunol. 1990; 125(1):197-209. DOI: 10.1016/0008-8749(90)90074-2. View

16.

Splawski J, McAnally L, Lipsky P . IL-2 dependence of the promotion of human B cell differentiation by IL-6 (BSF-2). J Immunol. 1990; 144(2):562-9. View

17.

Levy Y, Fermand J, Navarro S, Schmitt C, Vainchenker W, SELIGMANN M . Interleukin 6 dependence of spontaneous in vitro differentiation of B cells from patients with IgM gammapathy. Proc Natl Acad Sci U S A. 1990; 87(9):3309-13. PMC: 53889. DOI: 10.1073/pnas.87.9.3309. View

18.

Patsouris E, Noel H, Lennert K . Lymphoplasmacytic/lymphoplasmacytoid immunocytoma with a high content of epithelioid cells. Histologic and immunohistochemical findings. Am J Surg Pathol. 1990; 14(7):660-70. DOI: 10.1097/00000478-199007000-00007. View

19.

Brandt S, Bodine D, Dunbar C, Nienhuis A . Dysregulated interleukin 6 expression produces a syndrome resembling Castleman's disease in mice. J Clin Invest. 1990; 86(2):592-9. PMC: 296765. DOI: 10.1172/JCI114749. View

20.

Kishimoto T . The biology of interleukin-6. Blood. 1989; 74(1):1-10. View