Preti and colleagues report that the serum interleukin-6 level is closely correlated with prognosis in patients with diffuse large-cell lymphoma [1]. We are intrigued by this report because we recently encountered two patients with Ki-1 (CD30) antigen-positive lymphoma (Ki-1 lymphoma) who had high serum interleukin-6 levels (180 pg/mL and 202 pg/mL; normal < 4 pg/mL) and an aggressive clinical course. Ki-1 lymphoma is a new disease recognized by its distinct morphologic features and reactivity to a monoclonal antibody to the Ki-1 molecule [2, 3]. It is classified as an anaplastic large-cell lymphoma in the revised European-American classification of lymphoid neoplasms and is considered to be a moderately aggressive but potentially curable disease [4]. One of our patients with Ki-1 lymphoma was a 40-year-old man with CD4-positive T-cell phenotype, and the other was a 53-year-old man with CD19-positive B-cell phenotype [5]. They died with disseminated disease 7 months and 1.5 months, respectively, after diagnosis, despite intensive combination chemotherapy with cyclophosphamide, adriamycin, vincristine, and prednisolone (Table 1).

To further investigate the nature of the disease, we attempted to culture the patients' lymphoma cells in vitro by using medium that contained interleukin-6, 10 to 20 ng/mL. Two continuously growing Ki-1 lymphoma cell lines-DL-95 (CD4⁺) and DL-110 (CD19⁺)-that were initially dependent on interleukin-6 were successfully established. No expression of interleukin-6 gene messenger RNA or production of interleukin-6 from these cells was seen. However, expression of messenger RNA of the interleukin-6 receptor gene was demonstrated in both cell lines by polymerase chain reaction analysis, and interleukin-6 was shown to stimulate the growth of Ki-1 lymphoma cells in vitro by a paracrine mechanism through the interleukin-6 receptor.

These results suggest that high serum levels of interleukin-6 played a role in the disseminated proliferation of lymphoma cells and aggressive clinical course in our patients. Further studies are necessary to elucidate the mechanism and significance of high serum interleukin-6 levels in Ki-1 lymphoma. Monitoring of serum interleukin-6 levels may predict early disease progression, and interleukin-6 antagonists would be of value in the treatment of this aggressive disease.