Interleukin-6 production in posttransplant lymphoproliferative disease.
IL-6, a multifunctional cytokine produced by monocytes, fibroblasts, and endothelial cells, promotes the growth of EBV-immortalized B cells in vitro and renders these cells tumorigenic in athymic mice. In the present study, serum/plasma IL-6 bioactivity was found to be abnormally elevated, albeit transiently, in 17 of 18 solid organ transplant recipients with posttransplant lymphoproliferative disease (PTLD), with a mean maximal level of 196.7 U/ml. This represents a 16.4 increase above the normal mean (11.3 U/ml). In contrast, only 3 of 10 solid organ transplant recipients with uncomplicated courses posttransplant had abnormally elevated serum/plasma IL-6 bioactivity (mean maximal level 41.4 U/ml, P = 0.0007). When transferred to single cell culture, the 11 PTLD tissues produced 640 to 1.25 x 10(6) IL-6 U/ml in the culture supernatant, with a mean maximal level of 35,025 IL-6 U/ml. Cell separation experiments demonstrated that the adherent cells, identified as non-B cells, were the principal source of IL-6 production in vitro by PTLD tissue. Control cultures of inflammatory lymphoid tissue negative for lymphoproliferative disease as well as of PBL from patients with acute EBV-induced infectious mononucleosis consistently produced < 10 IL-6 U/ml. Thus, IL-6 is produced at high levels by PTLD tissues and may play a critical role in the pathogenesis of PTLD.
Tosato
G
G
Laboratory of Immunology, Center for Biologics Evaluation and Research, Bethesda, Maryland 20892.
Jones
K
K
Breinig
M K
MK
McWilliams
H P
HP
McKnight
J L
JL
D000328:Adult; D001706:Biopsy; D001940:Breast / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects; D007223:Infant; D015850:Interleukin-6 / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*; D013154:Spleen / Q000378:metabolism; D013997:Time Factors
D015850:Interleukin-6