Abstract
The tissue-fixed macrophage is a key cellular element in the initiation and regulation of inflammation. Understanding the regulation of macrophage activation may provide valuable clues to the mechanisms involved in both beneficial and deleterious effects of inflammation. The lymphokine interferon-γ (IFN-γ) is capable of producing paradoxical immunoinflammatory effects. In the immunocompromised host it up-regulates a variety of immune functions and improves survival, but it is also capable of producing harmful effects by sensitizing immunocompetent animals to subclinical doses of endotoxin. These paradoxical effects suggest that the state of activation or priming of the host immune system is a key determinant of its response to endotoxemia. Because tumor necrosis factor (TNF) and procoagulant activity (PCA) elaboration by the tissue-fixed macrophage play a central role in the host response to endotoxin, we asked whether the paradoxical effects of IFN-γ may be caused by priming of the macrophage for TNF and/or PCA production. In vitro, IFN-γ produces a marked augmentation in TNF but does not alter PCA elaboration in response to endotoxin, demonstrating the selectivity of IFN-γ priming of the macrophage. In vivo, IFN-γ pretreatment followed by an established subclinical endotoxin exposure enhances toxicity while simultaneously increasing peak serum TNF levels. Exogenous priming by IFN-γ alters the activation state of the macrophage and modifies the host response to endotoxin. Because this response is also dependent on the host's underlying immune state, IFN-γ treatment in the immunocompetent host has the potential to produce deleterious effects by eliciting an exaggerated TNF response during endotoxemia.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 579-584 |
| Number of pages | 6 |
| Journal | Journal of Leukocyte Biology |
| Volume | 52 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jan 1 1992 |
| Externally published | Yes |
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Keywords
- alveolar macrophage
- interferon-γ
- procoagulant activity
- tumor necrosis factor
ASJC Scopus subject areas
- Immunology
- Cell Biology
Cite this
Macrophage priming by interferon gamma : A selective process with potentially harmful effects. / Williams, J. G.; Jurkovich, Gregory; Hahnel, G. B.; Maier, R. V.
In: Journal of Leukocyte Biology, Vol. 52, No. 6, 01.01.1992, p. 579-584.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Macrophage priming by interferon gamma
T2 - A selective process with potentially harmful effects
AU - Williams, J. G.
AU - Jurkovich, Gregory
AU - Hahnel, G. B.
AU - Maier, R. V.
PY - 1992/1/1
Y1 - 1992/1/1
N2 - The tissue-fixed macrophage is a key cellular element in the initiation and regulation of inflammation. Understanding the regulation of macrophage activation may provide valuable clues to the mechanisms involved in both beneficial and deleterious effects of inflammation. The lymphokine interferon-γ (IFN-γ) is capable of producing paradoxical immunoinflammatory effects. In the immunocompromised host it up-regulates a variety of immune functions and improves survival, but it is also capable of producing harmful effects by sensitizing immunocompetent animals to subclinical doses of endotoxin. These paradoxical effects suggest that the state of activation or priming of the host immune system is a key determinant of its response to endotoxemia. Because tumor necrosis factor (TNF) and procoagulant activity (PCA) elaboration by the tissue-fixed macrophage play a central role in the host response to endotoxin, we asked whether the paradoxical effects of IFN-γ may be caused by priming of the macrophage for TNF and/or PCA production. In vitro, IFN-γ produces a marked augmentation in TNF but does not alter PCA elaboration in response to endotoxin, demonstrating the selectivity of IFN-γ priming of the macrophage. In vivo, IFN-γ pretreatment followed by an established subclinical endotoxin exposure enhances toxicity while simultaneously increasing peak serum TNF levels. Exogenous priming by IFN-γ alters the activation state of the macrophage and modifies the host response to endotoxin. Because this response is also dependent on the host's underlying immune state, IFN-γ treatment in the immunocompetent host has the potential to produce deleterious effects by eliciting an exaggerated TNF response during endotoxemia.
AB - The tissue-fixed macrophage is a key cellular element in the initiation and regulation of inflammation. Understanding the regulation of macrophage activation may provide valuable clues to the mechanisms involved in both beneficial and deleterious effects of inflammation. The lymphokine interferon-γ (IFN-γ) is capable of producing paradoxical immunoinflammatory effects. In the immunocompromised host it up-regulates a variety of immune functions and improves survival, but it is also capable of producing harmful effects by sensitizing immunocompetent animals to subclinical doses of endotoxin. These paradoxical effects suggest that the state of activation or priming of the host immune system is a key determinant of its response to endotoxemia. Because tumor necrosis factor (TNF) and procoagulant activity (PCA) elaboration by the tissue-fixed macrophage play a central role in the host response to endotoxin, we asked whether the paradoxical effects of IFN-γ may be caused by priming of the macrophage for TNF and/or PCA production. In vitro, IFN-γ produces a marked augmentation in TNF but does not alter PCA elaboration in response to endotoxin, demonstrating the selectivity of IFN-γ priming of the macrophage. In vivo, IFN-γ pretreatment followed by an established subclinical endotoxin exposure enhances toxicity while simultaneously increasing peak serum TNF levels. Exogenous priming by IFN-γ alters the activation state of the macrophage and modifies the host response to endotoxin. Because this response is also dependent on the host's underlying immune state, IFN-γ treatment in the immunocompetent host has the potential to produce deleterious effects by eliciting an exaggerated TNF response during endotoxemia.
KW - alveolar macrophage
KW - interferon-γ
KW - procoagulant activity
KW - tumor necrosis factor
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UR - http://www.scopus.com/inward/citedby.url?scp=0027092603&partnerID=8YFLogxK
U2 - 10.1002/jlb.52.6.579
DO - 10.1002/jlb.52.6.579
M3 - Article
C2 - 1464730
AN - SCOPUS:0027092603
VL - 52
SP - 579
EP - 584
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 6
ER -