Role of interleukin-6 in the paraneoplastic inflammatory syndrome associated with renal-cell carcinoma.
We investigated the possible causative role of interleukin 6 (IL-6) in the paraneoplastic inflammatory syndrome and in paraneoplastic cholestasis (Stauffer syndrome) associated with renal-cell carcinoma in a series of 119 patients with metastases. IL-6 levels were found significantly higher in patients with paraneoplastic fever and weight loss. Patients with detectable serum IL-6 (n = 90, 76%) had significantly higher serum CRP, haptoglobin, and serum alkaline-phosphatase and gammaglutamyl-transferase levels. Platelets, polymorphonuclear neutrophil (PMN) and monocyte counts were also significantly higher in patients with detectable serum IL-6; in contrast, hemoglobin levels were significantly lower in patients with serum IL-6 over 80 pg/ml. Three of these patients were included in a phase-II trial of an anti-IL-6 monoclonal antibody given daily during 21 days. Reductions of CRP, haptoglobin and serum alkalin phosphatases were observed in all 3 patients during anti-IL-6 administration, with a subsequent increase up to or above pre-treatment levels after the end of anti-IL-6. Decrease of platelets, PMN and monocyte counts were also observed in the 3 patients during anti-IL-6 administration, with a normalization of cell counts in a patient with increased platelets, PMN and monocyte counts. Hemoglobin concentration, serum albumin concentration and lymphocyte counts remained stable in the 3 patients during and after anti-IL-6 administration. Serum IL-6, as evaluated by IRMA, decreased in the 3 patients during anti-IL-6 administration, but increased above pre-treatment levels after the end of anti-IL-6 administration. These results demonstrate that IL-6 is involved in the physiopathology of paraneoplastic syndromes observed in patients with metastatic renal-cell carcinoma, in particular CRP and haptoglobin increase, paraneoplastic cholestasis, also paraneoplastic thrombocytosis, neutrophilia and monocytosis.
Blay
J Y
JY
Unite Cytokine et Cancer et Département de Médecine, Centre Léon Bérard, Lyon, France. blay@lyon.fnclcc.fr
Rossi
J F
JF
Wijdenes
J
J
Menetrier-Caux
C
C
Schemann
S
S
Négrier
S
S
Philip
T
T
Favrot
M
M
D000469:Alkaline Phosphatase / Q000097:blood; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000150:complications*; D002779:Cholestasis / Q000209:etiology; D005260:Female; D006242:Haptoglobins / Q000378:metabolism; D006801:Humans; D015592:Immunoradiometric Assay; D007249:Inflammation / Q000209:etiology*; D015850:Interleukin-6 / Q000276:immunology / Q000502:physiology*; D007680:Kidney Neoplasms / Q000097:blood / Q000150:complications*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010257:Paraneoplastic Syndromes / Q000209:etiology*; D010976:Platelet Count; D000093242:Interleukin-6 Inhibitors
D000469:Alkaline Phosphatase; D000911:Antibodies, Monoclonal; D002097:C-Reactive Protein; D006242:Haptoglobins; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors