Immunomodulatory and hematopoietic effects of recombinant human interleukin-6 in patients with advanced renal cell cancer.
Interleukin-6 (IL-6) is a cytokine with pleiotropic biologic activities on B cells, T cells, and hematopoietic progenitors. The present study was undertaken to assess pharmacodynamic effects of subcutaneous administration of IL-6 on blood counts, immunologic parameters, and acute-phase reactants. Blood samples were taken from patients with advanced renal cell cancer participating in a phase II trial of recombinant human IL-6. Multiparameter FACS analyses of peripheral blood mononuclear cells were performed using antibodies against CD3, CD4, CD8, HLA-DR, CD56, CD28, CD38, CD19, sIgM, and sIgG. Serum levels of IL-10, soluble CD23 (sCD23), sCD25, IL-1 receptor antagonist protein (IL-1RA), soluble tumor necrosis factor (TNF) receptors (sTNF-R) p55 and p75, and soluble IL-6 receptor (sIL-6R) were detected by ELISA systems. Levels of C-reactive protein (CRP), neopterin, fibrinogen, beta 2-microglobulin, and immunoglobulins M, G, and A were measured by standard methods. In response to administration of IL-6, a significant increment in platelet counts was observed, reaching peak levels after 21 days of treatment. In contrast, leukocyte subsets remained unaffected. No change in number of immunophenotype of peripheral blood B cells, T cells, or natural killer cells could be detected following IL-6 administration. Blood levels of sCD23, IL-10, sIL-6R, neopterin, beta 2-microglobulin, and immunoglobulin subsets were not influenced by cytokine therapy. However, administration of IL-6 led to a slow increment of acute-phase reactants CRP and fibrinogen. Furthermore, the anti-inflammatory molecules sTNF-R p55 and p75 were induced by IL-6, whereas serum levels of IL-1RA remained unchanged. Finally, an increase in blood levels of sCD25 was observed. In conclusion, IL-6 in vivo predominantly acts as a regulator of inflammation and a megakaryocyte differentiation factor.
Schuler
M
M
Department of Medicine III, Johannes Gutenberg University, Mainz, Germany.
Peschel
C
C
Schneller
F
F
Fichtner
J
J
Färber
L
L
Huber
C
C
Aulitzky
W E
WE
D000210:Acute-Phase Reaction; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D001772:Blood Cell Count / Q000187:drug effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D015850:Interleukin-6; D011994:Recombinant Proteins