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

doi:10.1016/j.clim.2006.03.003

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 journal › Article › peer-review

19 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 language	English
Pages (from-to)	129-137
Number of pages	9
Journal	Clinical Immunology
Volume	120
Issue number	2
DOIs	https://doi.org/10.1016/j.clim.2006.03.003
Publication status	Published - Aug 2006

Keywords

CRP
Immune modulation
rhIL-11
sTNFR

ASJC Scopus subject areas

Immunology and Allergy
Immunology

Access to Document

10.1016/j.clim.2006.03.003

Cite this

Ellis, M., Hedstrom, U., Frampton, C., Alizadeh, H., Kristensen, J., Shammas, F. V., & al-Ramadi, B. K. (2006). Modulation of the systemic inflammatory response by recombinant human interleukin-11: A prospective randomized placebo controlled clinical study in patients with hematological malignancy. Clinical Immunology, 120(2), 129-137. https://doi.org/10.1016/j.clim.2006.03.003

Modulation of the systemic inflammatory response by recombinant human interleukin-11: A prospective randomized placebo controlled clinical study in patients with hematological malignancy. / Ellis, Michael; Hedstrom, Ulla; Frampton, Chris et al.
In: Clinical Immunology, Vol. 120, No. 2, 08.2006, p. 129-137.

Research output: Contribution to journal › Article › peer-review

Ellis, M, Hedstrom, U, Frampton, C, Alizadeh, H, Kristensen, J, Shammas, FV & al-Ramadi, BK 2006, 'Modulation of the systemic inflammatory response by recombinant human interleukin-11: A prospective randomized placebo controlled clinical study in patients with hematological malignancy', Clinical Immunology, vol. 120, no. 2, pp. 129-137. https://doi.org/10.1016/j.clim.2006.03.003

@article{719c9eb20fa0468fbbf031577f870754,

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

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.",

keywords = "CRP, Immune modulation, rhIL-11, sTNFR",

author = "Michael Ellis and Ulla Hedstrom and Chris Frampton and Hussain Alizadeh and Jorgen Kristensen and Shammas, {Fuad V.} and al-Ramadi, {Basel K.}",

note = "Funding Information: We greatly acknowledge the expertise of Mr. A. Ullah for performing the laboratory analyses. We are grateful to Jan O'Brien, Senior Nurse and her nursing staff at Tawam Hospital for their support in this study. This study was supported by a grant from the Terry Fox Cancer Research Fund.",

year = "2006",

month = aug,

doi = "10.1016/j.clim.2006.03.003",

language = "English",

volume = "120",

pages = "129--137",

journal = "Clinical Immunology",

issn = "1521-6616",

publisher = "Academic Press Inc.",

number = "2",

}

TY - JOUR

T1 - Modulation of the systemic inflammatory response by recombinant human interleukin-11

T2 - A prospective randomized placebo controlled clinical study in patients with hematological malignancy

AU - Ellis, Michael

AU - Hedstrom, Ulla

AU - Frampton, Chris

AU - Alizadeh, Hussain

AU - Kristensen, Jorgen

AU - Shammas, Fuad V.

AU - al-Ramadi, Basel K.

N1 - Funding Information: We greatly acknowledge the expertise of Mr. A. Ullah for performing the laboratory analyses. We are grateful to Jan O'Brien, Senior Nurse and her nursing staff at Tawam Hospital for their support in this study. This study was supported by a grant from the Terry Fox Cancer Research Fund.

PY - 2006/8

Y1 - 2006/8

N2 - 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.

AB - 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.

KW - CRP

KW - Immune modulation

KW - rhIL-11

KW - sTNFR

UR - http://www.scopus.com/inward/record.url?scp=33746078414&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33746078414&partnerID=8YFLogxK

U2 - 10.1016/j.clim.2006.03.003

DO - 10.1016/j.clim.2006.03.003

M3 - Article

C2 - 16644288

AN - SCOPUS:33746078414

SN - 1521-6616

VL - 120

SP - 129

EP - 137

JO - Clinical Immunology

JF - Clinical Immunology

IS - 2

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this