The modulatory impact of recombinant human interleukin-6 on the immune system of cancer patients

To investigate the immunomodulatory impact of low-dose recombinant human in terleukin-6 (rhIL-6), we examined 15 patients with metastatic renal cell ca rcinoma or malignant melanoma receiving rhIL-6 as an antitumor agent in a p hase II trial. RhIL-6 (150 mu g) was administered subcutaneously (s.c.) onc e daily for 42 consecutive days. Immunologic parameters were measured throu ghout therapy and at follow-up. No changes in white blood cell counts were noted. Lymphocyte subsets did not alter, nor did their expression of CD25 a nd HLA-DR. Immunoglobulins were unaffected. Levels of granulocyte-macrophag e colony-stimulating factor, tumor necrosis factor-alpha and IL-1 beta rema ined below detection limits. Theoretically, subtle immunologic alterations might have been masked by increases in plasma volume, known tc occur after start of therapy. Using previously published data concerning plasma volume changes in these patients, part of immunologic data were corrected for conc urrent hemodilution, showing a 39% +/- 17% increase in monocytes (mean chan ge +/- SEM [standard error of mean]; p < 0.03) within 1 week of therapy, wh ile lymphocytes tended to increase. However, the absence of appreciable inc reases in cell activation markers and in monokine levels indicates insuffic ient immune activation, probably underlying the lack of objective antitumor responses (6 x stable, 9 x progressive disease) in these patients. In conc lusion, the immunomodulatory impact of rhIL-6, if present at all, remains v ery limited.