Role of interleukin-6 in the Paraneoplastic Inflammatory Syndrome Associated With Renal-Cell Carcinoma

Int J Cancer. 1997 Jul 29;72(3):424-30. doi: 10.1002/(sici)1097-0215(19970729)72:3<424::aid-ijc9>3.0.co;2-r.

Abstract

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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / blood
  • Antibodies, Monoclonal / therapeutic use
  • C-Reactive Protein / metabolism
  • Carcinoma, Renal Cell / blood
  • Carcinoma, Renal Cell / complications*
  • Cholestasis / etiology
  • Female
  • Haptoglobins / metabolism
  • Humans
  • Immunoradiometric Assay
  • Inflammation / etiology*
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / immunology
  • Interleukin-6 / physiology*
  • Kidney Neoplasms / blood
  • Kidney Neoplasms / complications*
  • Leukocyte Count
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Paraneoplastic Syndromes / etiology*
  • Platelet Count

Substances

  • Antibodies, Monoclonal
  • Haptoglobins
  • Interleukin-6
  • C-Reactive Protein
  • Alkaline Phosphatase