Modulation of the systemic inflammatory response by recombinant human interleukin-11: A prospective randomized placebo controlled clinical study in patients with hematological malignancy

Michael Ellis, Ulla Hedstrom, Chris Frampton, Hussain Alizadeh, Jorgen Kristensen, Fuad V. Shammas, Basel K. al-Ramadi

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

The immunomodulatory activities of recombinant human interleukin-11 (rhIL-11) were investigated in a clinical trial among patients with hematological malignancy, randomized to either rhIL-11 or placebo throughout chemotherapy. Daily serum concentrations of sTNFRI, IL-6, IL-8, TNFα, and CRP were measured. Higher sTNFRI levels [mean pg/ml (95% CI)] were detected in patients receiving rhIL-11 compared to placebo [1749.7 (1626-1882.9) versus 1038.5 (953.3-1131.3)] respectively (P = 0.01) for all 898 observations and during febrile days [2327.6 (2142.6-2528.2) versus 1308.9 (1163-1473.2), P = 0.12] and during days without infection [1406.6 (1266.1-1563) versus 871.3 (774.9-979.6), P < 0.001]. A similar pattern in CRP concentrations was observed. Multivariate analysis indicated rhIL-11 was associated with elevated sTNFRI or CRP independent of infectious episodes and other factors. 7 patients (all receiving placebo) of 40 had elevated TNFα levels. IL-6 and IL-8 levels were not substantially affected by rhIL-11. Bacteremia, fungal infections, and fever of unknown origin (FUO) were reduced in rhIL-11-treated patients. Given the role of sTNFRI in dampening the deleterious effects of a hyperactive TNFα environment, rhIL-11-induced upregulation of sTNFRI shedding is a potentially important mechanism for modulating immune and inflammatory responses in humans.

Original languageEnglish
Pages (from-to)129-137
Number of pages9
JournalClinical Immunology
Volume120
Issue number2
DOIs
Publication statusPublished - Aug 2006

Keywords

  • CRP
  • Immune modulation
  • rhIL-11
  • sTNFR

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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