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 interleukin-6 (rhIL-6), we examined 15 patients with metastatic renal cell carcinoma or malignant melanoma receiving rhIL-6 as an antitumor agent in a phase II trial. RhIL-6 (150 micrograms) was administered subcutaneously (s.c.) once daily for 42 consecutive days. Immunologic parameters were measured throughout 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 and HLA-DR. Immunoglobulins were unaffected. Levels of granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha and IL-1 beta remained below detection limits. Theoretically, subtle immunologic alterations might have been masked by increases in plasma volume, known to occur after start of therapy. Using previously published data concerning plasma volume changes in these patients, part of immunologic data were corrected for concurrent hemodilution, showing a 39% +/- 17% increase in monocytes (mean change +/- SEM [standard error of mean]; p < 0.03) within 1 week of therapy, while lymphocytes tended to increase. However, the absence of appreciable increases in cell activation markers and in monokine levels indicates insufficient immune activation, probably underlying the lack of objective antitumor responses (6 x stable, 9 x progressive disease) in these patients. In conclusion, the immunomodulatory impact of rhIL-6, if present at all, remains very limited.
Division of Medical Oncology, University Hospital, Groningen, The Netherlands.
J
J
Nieken
N H
NH
Mulder
J
J
Pietens
P C
PC
Limburg
L
L
de Leij
E G
EG
de Vries
D000293:Adolescent; D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D016207:Cytokines / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood / Q000187:drug effects; D006801:Humans; D007136:Immunoglobulins / Q000097:blood / Q000187:drug effects; D015850:Interleukin-6 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D007958:Leukocyte Count; D016131:Lymphocyte Subsets; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D008875:Middle Aged; D011379:Prognosis; D011994:Recombinant Proteins / Q000627:therapeutic use; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000187:drug effects
D016207:Cytokines; D007136:Immunoglobulins; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor