Pathogenic significance of interleukin-6 in angioimmunoblastic lymphadenopathy-type T-cell lymphoma.
Patients with angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma may develop hypergammaglobulinemia. Among four cases of AILD-type T-cell lymphoma that we have studied, we detected a correlation between the number of plasma cells in tissue and the extent of interleukin-6 (IL-6) expression in lymphoma cells. We did not detect IL-6 in three patients who had no hypergammaglobulinemia and whose tissues showed only minimal plasma cell infiltration. In the fourth patient we observed an abundant IL-6 production by lymphoma cells, which accounted for a B-cell plasmacytic tissue response and for hypergammaglobulinemia. The pathogenic significance of IL-6 was substantiated by a concomitant decrease in the serum IL-6 level, measurable tumor mass, and immunoglobulin levels, as well as by a decline in the proportion of plasmacytoid cells in peripheral blood promptly on administration of chemotherapy. Plasmacytoid B cells could be maintained in culture in the presence of IL-6, but viability was lost on co-incubation with anti-IL-6. Interleukin-1 and tumor necrosis factor were not produced by T lymphoma cells and were incapable of sustaining plasmacytoid B-cell viability in vitro. Small amounts of IL-4 were noted in T lymphoma cells. Thus, in this case of AILD-type T-cell lymphoma, tumor cells with a T-cell phenotype produced IL-6 in large quantities, explaining the accompanying B-cell and plasmacytic histologic changes and humoral disease manifestations, including marked hypergammaglobulinemia. Although not all cases of AILD-type T-cell lymphoma have an accompanying plasma cell proliferation and hypergammaglobulinemia, and although the cytokine network in these patients may be more complex than has been recognized, this case with IL-6 expression serves to illustrate the utility of cytokine assays in the analysis of the histopathologic and clinical heterogeneities of peripheral T-cell lymphomas.
Hsu
S M
SM
Department of Pathology, University of Arkansas for Medical Sciences, Arkansas Cancer Research Center, Little Rock.
Waldron
J A
JA
Fink
L
L
King
C
C
Xie
S S
SS
Mansouri
A
A
Barlogie
B
B
D000368:Aged; D001853:Bone Marrow / Q000473:pathology; D002097:C-Reactive Protein / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007119:Immunoblastic Lymphadenopathy / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D007136:Immunoglobulins / Q000032:analysis; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism*; D016399:Lymphoma, T-Cell / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D007136:Immunoglobulins; D015850:Interleukin-6; D002097:C-Reactive Protein