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Interferon γ increases sensitivity to endotoxin

Interferon γ increases sensitivity to endotoxin

Authors :
Charles L. Rice
Gregory J. Jurkovich
Ronald V. Maier
William J. Mileski
Robert K. Winn
Source :
Journal of Surgical Research. 51:197-203
Publication Year :
1991
Publisher :
Elsevier BV, 1991.

Abstract

Interferon-γ (IFN-γ) has been proposed for use following severe trauma to reverse depressed macrophage (Mφ) function and thereby reduce infection, sepsis, and subsequent multiple organ failure syndrome (MOFS). However, an excessive inflammatory response by Mφs and other components of the inflammatory cascade is thought to be central to the underlying pathophysiology of MOFS. Endotoxin (LPS) has been implicated as a principal mediator of sepsis-induced MOFS by stimulating Mφs and leukocytes (WBC). This study addresses the following question: Does IFN-γ predispose normal rabbits to a pathophysiologic response to LPS infusion? Four groups of New Zealand White rabbits ( n = 6, each group) were prepared for measurement of cardiac output, arterial pressure, arterial PO 2 , and WBC counts over a 6-hr period. Group I (control) was instrumented alone, Group II (LPS alone) was given a subclinical dose of 1.0 μg/kg of Escherichia coli LPS iv, Group III (IFN-γ alone) was given recombinant rabbit IFN-γ (5.0 μg/kg subcutaneous) for 3 days prior to preparation for measurements, and Group IV (IFN-γ + LPS) received 3 days of IFN-γ followed by LPS. One hour prior to sacrifice 5.0 μCi of 125 I-albumin was given and bronchoalveolar lavage was performed at death to determine the lavage/plasma 125 I ratio as an index of pulmonary permeability. The results indicate that IFN + LPS animals had significant decreases in cardiac output, PO 2 , and WBC counts, and increased lavage/plasma ratio of 125 I-albumin when compared to all other groups ( P t test). Neither LPS alone nor IFN-γ alone had a significant effect on measured variables. In contrast to immunosuppressed animals, IFN-γ pretreatment of normal animals increases the host pathophysiologic response to endotoxin.

Details

ISSN :
00224804
Volume :
51
Database :
OpenAIRE
Journal :
Journal of Surgical Research
Accession number :
edsair.doi.dedup.....04f72836e21aee73f8537855c5a34631
Full Text :
https://doi.org/10.1016/0022-4804(91)90094-3