The activation of polymorphonuclear neutrophils and the complement system during immunotherapy with recombinant interleukin-2

J. W. Baars; C. E. Hack; J. Wagstaff; A. J M Eerenberg-Belmer; G. J. Wolbink; L. G. Thijs; R. J M Strack van Schijndel; H. L J A van der Vall; H. M. Pinedo

The activation of polymorphonuclear neutrophils and the complement system during immunotherapy with recombinant interleukin-2

J. W. Baars, C. E. Hack, J. Wagstaff, A. J M Eerenberg-Belmer, G. J. Wolbink, L. G. Thijs, R. J M Strack van Schijndel, H. L J A van der Vall, H. M. Pinedo

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

38 Scopus citations

Abstract

The toxicity due to interleukin-2 (IL-2) strongly resembles the clinical picture seen during septic shock. In septic shock activation of polymorphonuclear neutrophils (PMN) and the complement system contribute significantly to the pathophysiology of the condition. We therefore investigated whether similar events contributed to the toxicity observed with IL-2. Four patients received seven cycles of escalating dose IL-2 (18.0 to 72.0 x 10⁶ 1Um^-2 day^-1) and 16 were treated with 20 cycles of fixed dose IL-2 (12.0 or 18.0 x 10⁶ 1Um^-2 day^-1). Toxicity, as judged by hypotension (P=-1; P=1A) and lactoferrin values of 212 (SEM=37) and 534 (SEM=92) ng ml^-1 respectively occurring 6h after the IL-2. Peak values for the esc. dose IL-2 group being generally higher than 500ng ml^-1. Activation of thc complement cascade was evidenced by a dose dependent elevation of peak C3a values (fixed dose 9.1 (SEM=0.6), esc. dose 25.7 (SEM=6.33); P=

Original language	English (US)
Pages (from-to)	96-101
Number of pages	6
Journal	British Journal of Cancer
Volume	65
Issue number	1
State	Published - 1992
Externally published	Yes

ASJC Scopus subject areas

Cancer Research
Oncology

Cite this

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title = "The activation of polymorphonuclear neutrophils and the complement system during immunotherapy with recombinant interleukin-2",

abstract = "The toxicity due to interleukin-2 (IL-2) strongly resembles the clinical picture seen during septic shock. In septic shock activation of polymorphonuclear neutrophils (PMN) and the complement system contribute significantly to the pathophysiology of the condition. We therefore investigated whether similar events contributed to the toxicity observed with IL-2. Four patients received seven cycles of escalating dose IL-2 (18.0 to 72.0 x 106 1Um-2 day-1) and 16 were treated with 20 cycles of fixed dose IL-2 (12.0 or 18.0 x 106 1Um-2 day-1). Toxicity, as judged by hypotension (P=-1; P=1A) and lactoferrin values of 212 (SEM=37) and 534 (SEM=92) ng ml-1 respectively occurring 6h after the IL-2. Peak values for the esc. dose IL-2 group being generally higher than 500ng ml-1. Activation of thc complement cascade was evidenced by a dose dependent elevation of peak C3a values (fixed dose 9.1 (SEM=0.6), esc. dose 25.7 (SEM=6.33); P=",

author = "Baars, {J. W.} and Hack, {C. E.} and J. Wagstaff and Eerenberg-Belmer, {A. J M} and Wolbink, {G. J.} and Thijs, {L. G.} and {Strack van Schijndel}, {R. J M} and {van der Vall}, {H. L J A} and Pinedo, {H. M.}",

year = "1992",

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pages = "96--101",

journal = "British Journal of Cancer",

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T1 - The activation of polymorphonuclear neutrophils and the complement system during immunotherapy with recombinant interleukin-2

AU - Baars, J. W.

AU - Hack, C. E.

AU - Wagstaff, J.

AU - Eerenberg-Belmer, A. J M

AU - Wolbink, G. J.

AU - Thijs, L. G.

AU - Strack van Schijndel, R. J M

AU - van der Vall, H. L J A

AU - Pinedo, H. M.

PY - 1992

Y1 - 1992

N2 - The toxicity due to interleukin-2 (IL-2) strongly resembles the clinical picture seen during septic shock. In septic shock activation of polymorphonuclear neutrophils (PMN) and the complement system contribute significantly to the pathophysiology of the condition. We therefore investigated whether similar events contributed to the toxicity observed with IL-2. Four patients received seven cycles of escalating dose IL-2 (18.0 to 72.0 x 106 1Um-2 day-1) and 16 were treated with 20 cycles of fixed dose IL-2 (12.0 or 18.0 x 106 1Um-2 day-1). Toxicity, as judged by hypotension (P=-1; P=1A) and lactoferrin values of 212 (SEM=37) and 534 (SEM=92) ng ml-1 respectively occurring 6h after the IL-2. Peak values for the esc. dose IL-2 group being generally higher than 500ng ml-1. Activation of thc complement cascade was evidenced by a dose dependent elevation of peak C3a values (fixed dose 9.1 (SEM=0.6), esc. dose 25.7 (SEM=6.33); P=

AB - The toxicity due to interleukin-2 (IL-2) strongly resembles the clinical picture seen during septic shock. In septic shock activation of polymorphonuclear neutrophils (PMN) and the complement system contribute significantly to the pathophysiology of the condition. We therefore investigated whether similar events contributed to the toxicity observed with IL-2. Four patients received seven cycles of escalating dose IL-2 (18.0 to 72.0 x 106 1Um-2 day-1) and 16 were treated with 20 cycles of fixed dose IL-2 (12.0 or 18.0 x 106 1Um-2 day-1). Toxicity, as judged by hypotension (P=-1; P=1A) and lactoferrin values of 212 (SEM=37) and 534 (SEM=92) ng ml-1 respectively occurring 6h after the IL-2. Peak values for the esc. dose IL-2 group being generally higher than 500ng ml-1. Activation of thc complement cascade was evidenced by a dose dependent elevation of peak C3a values (fixed dose 9.1 (SEM=0.6), esc. dose 25.7 (SEM=6.33); P=

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The activation of polymorphonuclear neutrophils and the complement system during immunotherapy with recombinant interleukin-2

Abstract

ASJC Scopus subject areas

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