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Ki-Lymphoma and Interleukin-6
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IN RESPONSE:
Dr. Kubonishi and colleagues describe high serum levels of interleukin-6 in two patients with aggressive Ki-1 lymphoma. They further demonstrate that expression of interleukin-6 RNA and protein is absent in cell lines derived from these two patients, whereas expression of RNA for the interleukin-6 receptor is present. In addition, interleukin-6 could stimulate proliferation of the patients' lymphoma cells in vitro, suggesting a paracrine growth mechanism.
These results are of interest. We have shown that high serum interleukin-6 levels are present and that they correlate with poor prognosis in both Hodgkin and non-Hodgkin lymphoma [1-3]. Indeed, in diffuse large-cell lymphoma, interleukin-6 seems to be the most significant independent prognostic variable selected by multivariate analysis for prediction of both complete remission and failure-free survival [3]. Whether an autocrine or a paracrine mechanism is most significant is unclear, but both may be operative. For instance, Voorzanger and associates [4] used immunohistochemical methods to show that 89% of the non-Hodgkin lymphoma tumor samples that they studied were positive for interleukin-6 expression in both tumor cells and macrophages. Yee and coworkers [5] have shown interleukin-6 production and the use of interleukin-6 in an autocrine fashion for growth in two lymphoma cell lines. Taken together, these data suggest 1) an autocrine and paracrine role for endogenous interleukin-6 in lymphoma and 2) that the contribution of these alternative mechanisms to tumor proliferation may vary from patient to patient and between lymphoma subtypes. Future investigations should aim to identify the prognostic value of interleukin-6 in other lymphoproliferative disorders, to determine whether serum interleukin-6 levels can predict early relapse, and to develop interleukin-6 antagonists for the treatment of these lymphomas.
Razelle Kurzrock, MD
University of Texas M.D. Anderson Cancer Center; Houston, TX 77030
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
