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Vasoactive side effects of intravenous immunoglobulin preparations in a rat model and their treatment with recombinant platelet-activating factor acetylhydrolase

Vasoactive side effects of intravenous immunoglobulin preparations in a rat model and their treatment with recombinant platelet-activating factor acetylhydrolase
Vasoactive side effects of intravenous immunoglobulin preparations in a rat model and their treatment with recombinant platelet-activating factor acetylhydrolase
Previously, we observed in a rat model that intravenous administration of intramuscular immunoglobulin preparations induced a long-lasting hypotension, which appeared to be associated with the presence of IgG polymers and dimers in the preparations, but unrelated to complement activation. We found evidence that this hypotensive response is mediated by platelet-activating factor (PAF) produced by macrophages.

In this study, we compared the vasoactive effects of 16 intravenous immunoglobulin (IVIG) products from 10 different manufacturers, in anesthetized rats. Eight of the IVIG preparations showed no hypotensive effects (less than 15% decrease), whereas the other 8 had relatively strong effects (15%-50% decrease). The hypotensive effects correlated with the IgG dimer content of the preparations. Pretreatment of the rats with recombinant PAF acetylhydrolase completely prevented the hypotensive reaction on IVIG infusion, and administration after the onset of hypotension resulted in normalization of the blood pressure.

We also observed PAF production on in vitro incubation of human neutrophils with IVIG, which could be blocked by anti-Fcgamma receptor antibodies. This indicates that induction of PAF generation may also occur in a human system. Our findings support the hypothesis that the clinical side effects of IVIG in patients may be caused by macrophage and neutrophil activation through interaction of IgG dimers with Fcgamma receptors.

Because phagocyte activation may also lead to the release of other inflammatory mediators, recombinant PAF acetylhydrolase (rPAF-AH) provides a useful tool to determine whether PAF plays a role in the clinical side effects of IVIG. If so, rPAF-AH can be used for the treatment of those adverse reactions.
0006-4971
1856-1861
Bleeker, Wim K.
6a6a8012-91b2-4b02-b216-2356c6959544
Teeling, Jessica L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Verhoeven, Arthur J.
85fb05b3-9043-4db4-bdf8-e89b90deb201
Rigter, Gemma M.M.
342db251-0622-4623-a1f8-03f178278bef
Agterberg, Jacques
3257ff77-bacf-4b27-9afa-94babdcd4685
Tool, Anton T.J.
5657e4a5-d708-4bda-ab8e-dfd24094e5fe
Koenderman, Anky H.L.
0b50d121-76d1-4e24-b684-a383bb45f283
Kuijpers, Taco W.
50817ff2-ecd2-4e90-9bd0-ebff8883cdd2
Hack, C. Erik
6d53e078-bda2-4def-bcef-48dc482384d2
Bleeker, Wim K.
6a6a8012-91b2-4b02-b216-2356c6959544
Teeling, Jessica L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Verhoeven, Arthur J.
85fb05b3-9043-4db4-bdf8-e89b90deb201
Rigter, Gemma M.M.
342db251-0622-4623-a1f8-03f178278bef
Agterberg, Jacques
3257ff77-bacf-4b27-9afa-94babdcd4685
Tool, Anton T.J.
5657e4a5-d708-4bda-ab8e-dfd24094e5fe
Koenderman, Anky H.L.
0b50d121-76d1-4e24-b684-a383bb45f283
Kuijpers, Taco W.
50817ff2-ecd2-4e90-9bd0-ebff8883cdd2
Hack, C. Erik
6d53e078-bda2-4def-bcef-48dc482384d2

Bleeker, Wim K., Teeling, Jessica L., Verhoeven, Arthur J., Rigter, Gemma M.M., Agterberg, Jacques, Tool, Anton T.J., Koenderman, Anky H.L., Kuijpers, Taco W. and Hack, C. Erik (2000) Vasoactive side effects of intravenous immunoglobulin preparations in a rat model and their treatment with recombinant platelet-activating factor acetylhydrolase. Blood, 95 (5), 1856-1861.

Record type: Article

Abstract

Previously, we observed in a rat model that intravenous administration of intramuscular immunoglobulin preparations induced a long-lasting hypotension, which appeared to be associated with the presence of IgG polymers and dimers in the preparations, but unrelated to complement activation. We found evidence that this hypotensive response is mediated by platelet-activating factor (PAF) produced by macrophages.

In this study, we compared the vasoactive effects of 16 intravenous immunoglobulin (IVIG) products from 10 different manufacturers, in anesthetized rats. Eight of the IVIG preparations showed no hypotensive effects (less than 15% decrease), whereas the other 8 had relatively strong effects (15%-50% decrease). The hypotensive effects correlated with the IgG dimer content of the preparations. Pretreatment of the rats with recombinant PAF acetylhydrolase completely prevented the hypotensive reaction on IVIG infusion, and administration after the onset of hypotension resulted in normalization of the blood pressure.

We also observed PAF production on in vitro incubation of human neutrophils with IVIG, which could be blocked by anti-Fcgamma receptor antibodies. This indicates that induction of PAF generation may also occur in a human system. Our findings support the hypothesis that the clinical side effects of IVIG in patients may be caused by macrophage and neutrophil activation through interaction of IgG dimers with Fcgamma receptors.

Because phagocyte activation may also lead to the release of other inflammatory mediators, recombinant PAF acetylhydrolase (rPAF-AH) provides a useful tool to determine whether PAF plays a role in the clinical side effects of IVIG. If so, rPAF-AH can be used for the treatment of those adverse reactions.

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Published date: 1 March 2000

Identifiers

Local EPrints ID: 153905
URI: https://eprints.soton.ac.uk/id/eprint/153905
ISSN: 0006-4971
PURE UUID: 30722cc9-7903-4b16-89f9-2249ad5a2476

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Date deposited: 26 Jul 2010 10:15
Last modified: 18 Jul 2017 12:47

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Contributors

Author: Wim K. Bleeker
Author: Arthur J. Verhoeven
Author: Gemma M.M. Rigter
Author: Jacques Agterberg
Author: Anton T.J. Tool
Author: Anky H.L. Koenderman
Author: Taco W. Kuijpers
Author: C. Erik Hack

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