Mechanisms of Altered Monocyte Prostaglandin E2 Production in Severely Injured Patients

Miller-Graziano, Carol L.; Fink, Mitchell P.; Wu, Jillian; Szabó, Gyöngyi; Kodys, Karen

doi:10.1001/archsurg.1988.01400270027003

Cited by 113 publications

(22 citation statements)

References 28 publications

(3 reference statements)

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“…Furthermore, PGE 2 can inhibit many aspects of macrophage function [48,49], and thermal injury also alters macrophage responses to PGE 2 [22,25]. Consistent with previous findings [24,50,51], macrophages from injured mice produced elevated amounts of PGE 2 . However, the lack of ␥␦ T lymphocytes did not modify the elevated PGE 2 response by macrophages post-burn, suggesting that the suppression in pro-inflammatory cytokine production observed in TCR ␦ -/-mice is independent of control by PGE 2 .…”

Section: Discussionsupporting

confidence: 67%

Insights into the role of γδ T lymphocytes in the immunopathogenic response to thermal injury

Schwacha

Ayala

Chaudry

2000

Journal of Leukocyte Biology

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Studies have shown that cell-mediated immunity is markedly suppressed after thermal injury. T lymphocyte dysfunction and macrophage hyperactivity have been implicated as causative factors. Previous studies have primarily examined the effects of thermal injury on ␣␤ T lymphocytes; however, the role of ␥␦ T lymphocytes in the immune response after thermal injury is unclear. Therefore, wild-type mice and mice lacking the TCR ␦ gene (TCR ␦ ؊/؊ ) were subjected to a thirddegree scald burn and cell-mediated immune responses assessed at 7 days post-injury. TCR ␦ ؊/؊ mice had 75% mortality after burn injury compared with 25% mortality in the wild-type group. Plasma interluekin-6 (IL-6) levels were significantly elevated at 2, 4, and 18 h post-injury, whereas no difference was observed in tumor necrosis factor ␣ (TNF-␣) and prostaglandin E 2 (PGE 2 ) plasma levels. Plasma levels of these inflammatory mediators were similar in wild-type and TCR ␦ ؊/؊ mice post-injury. Splenic macrophage PGE 2 , IL-6, TNF-␣, and IL-10 production was significantly increased in wild-type mice at 7 days post-injury, whereas macrophages from injured TCR ␦ ؊/؊ mice had a significantly attenuated capacity to produce IL-6 and TNF-␣. In contrast, the increased release of PGE 2 and IL-10 by macrophages post-injury was not reduced in TCR ␦ ؊/؊ mice. These results implicate a dual role for ␥␦ T lymphocytes in the immunopathogenic response to burn injury: (1) they contribute to survival from the insult; and (2) they mediate the induction of a pro-inflammatory macrophage phenotype at 7 days post-injury. Thus, ␥␦ T lymphocytes, in part through the modulation of macrophage activity, appear to contribute to the immune dysfunction after thermal injury. J. Leukoc. Biol. 67: 644-650; 2000.

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Section: Discussionsupporting

confidence: 67%

Insights into the role of γδ T lymphocytes in the immunopathogenic response to thermal injury

Schwacha

Ayala

Chaudry

2000

Journal of Leukocyte Biology

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“…Postoperative alterations in host immune functions after major surgery have been well described (1,7,17,18,25,26,39,42,44), and several studies have proposed a causal relationship between surgical or traumatic injury and the subsequent development of infectious complications (34,37). When delivered endotracheally, lipopolysaccharide (LPS) in the cell walls of gram-negative bacteria induces the release of TNF-␣ from pulmonary macrophages and neutrophils, and the resulting extensive inflammatory response is believed to be responsible, in part, for the high mortality associated with nosocomial infections (20).…”

Section: Discussionmentioning

confidence: 99%

“…Decreased production of IL-1and IL-2 and increased monocyte prostaglandin E 2 production after trauma have been suggested as two of the major monocyte dysfunctions that contribute to alterations in immune system responsiveness (16,17,44). Following injury or major surgery, elevated levels of prostaglandin E 2 in monocytes have been shown to suppress monocyte antigen-presenting capacity and T-cell expression of IL-2 (16)(17)(18), along with a loss of cell surface HLA-DR molecules (74).…”

mentioning

confidence: 99%

Bacterial Clearance and Cytokine Profiles in a Murine Model of Postsurgical Nosocomial Pneumonia

Manderscheid

Bodkin

Davidson

et al. 2004

Clin Vaccine Immunol

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The development of a nosocomial pneumonia is facilitated by alterations in host innate pulmonary antibacterial defenses following surgical trauma, which can result in decreased pulmonary bacterial clearance and increased morbidity and mortality. In a murine model of postoperative nosocomial infection, surgical stress (laparotomy) decreased Escherichia coli clearance from the lungs of animals that underwent surgery. Consistent with previous studies, (i) pulmonary levels of tumor necrosis factor alpha at 6 h and of interleukin-1␤ (IL-1␤), IL-6, and gamma interferon (IFN-␥) at 24 h post-bacterial infection (PBI) were decreased in animals that underwent laparotomy 24 h prior to E. coli infection (LAP/E. coli) compared to animals that received E. coli only; (ii) KC and macrophage inhibitory protein 2 were elevated at 6 h PBI in LAP/E. coli animals compared to E. coli-only animals; however, at 24 h PBI, levels were higher in the E. coli-only group; (iii) at 24 h PBI, monocyte chemoattractant protein 1 was lower in the LAP/E. coli group compared to the E. coli-only group; (iv) IL-10 levels were unaffected at all time points evaluated; and (v) the total number of neutrophils present in the lungs of LAP/E. coli animals at 6 h PBI was decreased in comparison to that in E. coli-only animals, resulting in decreased bacterial clearance and increased mortality in LAP/E. coli animals by 24 h PBI. Similar changes in cytokine profiles, pulmonary bacterial clearance, and mortality were consistent with reported findings in patients following surgical trauma. This model, therefore, provides a clinically relevant system in which the molecular and cellular mechanisms that lead to the development of nosocomial pneumonia can be further explored.

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“…Recent evidence suggests that the altered expression of M effector function is of fundamental importance in the development of the immunosuppressed state observed after thermal injury [4][5][6]. Burn injury alters M effector function leading to enhanced monokine [i.e., interleukin-1 (IL-1), tumor necrosis factor-␣ (TNF-␣), interleukin-6 (IL-6)] [7][8][9], reactive nitrogen intermediates [RNI] [4,10,11], and prostaglandin [7,12] production in vitro. Furthermore, elevated levels of these pro-inflammatory mediators have been observed systemically after thermal injury [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Thermal injury alters macrophage responses to prostaglandin E2: contribution to the enhancement of inducible nitric oxide synthase activity

Schwacha

Samy

Catania

et al. 1998

Journal of Leukocyte Biology

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Prostaglandin E 2 (PGE 2 ) and macrophage (M) -derived reactive nitrogen intermediates (RNI) have been implicated in T cell dysfunction after thermal injury. Normally, M inducible nitric oxide synthase (iNOS) activity can be regulated by PGE 2 , however, it is unknown whether PGE 2 modulates M iNOS activity after thermal injury. Splenic M isolated from mice 7 days after thermal injury produced higher levels of RNI than M from sham mice when stimulated with lipopolysaccharide (LPS) or interferon-␥ (IFN-␥) and tumor necrosis factor ␣ (TNF-␣) in combination. PGE 2 , when added concurrently with LPS, suppressed RNI production by M from sham mice, whereas M from injured mice were unaffected. When M were pretreated with PGE 2 before LPS, RNI production was suppressed in both populations. RNI production in response to IFN-␥ or IFN-␥ and TNF-␣ in combination was enhanced by PGE 2 in both populations, however, the effect was markedly greater in M from injured mice. The PGE 2 -mediated changes in RNI production were paralleled by similar changes in iNOS protein expression, suggesting that the effect of PGE 2 was at the level of enzyme expression rather than activity. Dibutryl cAMP induced similar effects as PGE 2 , suggesting the response to PGE 2 after thermal injury is independent of potential changes in PGE 2 -induced adenylate cyclase activity and is cAMPmediated. The results indicate that M from burned mice display an altered sensitivity to PGE 2 , resulting in enhanced iNOS activity. Thus, PGE 2 , which is elevated after thermal injury and can directly suppress T cell function, may also contribute to immune dysfunction through the enhancement of M iNOS activity. J. Leukoc. Biol. 64: 740-746; 1998.

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Mechanisms of Altered Monocyte Prostaglandin E2 Production in Severely Injured Patients

Cited by 113 publications

References 28 publications

Insights into the role of γδ T lymphocytes in the immunopathogenic response to thermal injury

Insights into the role of γδ T lymphocytes in the immunopathogenic response to thermal injury

Bacterial Clearance and Cytokine Profiles in a Murine Model of Postsurgical Nosocomial Pneumonia

Thermal injury alters macrophage responses to prostaglandin E2: contribution to the enhancement of inducible nitric oxide synthase activity

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