Mechanisms of immune failure in burn injury

Sparkes, B. G.

doi:10.1016/0264-410x(93)90218-m

Cited by 30 publications

(22 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Endotoxin is considered to be an important factor in the pathology of sepsis (a major complication after thermal injury). However, previous studies have shown that multiple organ failure and significant mortality in the absence of endotoxemia does occur [36,37].…”

Section: Discussionmentioning

confidence: 96%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 96%

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

View full text Add to dashboard Cite

show abstract

“…The production of these factors after burn is associated with decreased lymphocyte functions including proliferation, IL-2 production and IL-2R expression (Miller-Graziano et al 1991, 1993, Fukushima et al 1994, Horgan et al 1994a, Meert et al 1996, Gregory et al 2000c. Furthermore, exposure of macrophages to testosterone can increase production of TGF-directly (Benten et al 1999), and thus that of IL-6 and PGE 2 (MillerGraziano et al 1991, 1993, Olsen et al 1994. Therefore, an increase in the percentage of macrophages after injury would result in an exaggerated effect of these factors on lymphocyte function, which could be ameliorated by the administration of flutamide.…”

Section: Discussionmentioning

confidence: 99%

“…However, as the IL-2R expression was fully recovered, but proliferation and IL-2 production were only partially restored, it is unlikely that this change in IL-2R expression is relevant. In addition, in experiments demonstrating reduced IL-2R after injury, lymphocyte proliferation could be restored by the addition of exogenous IL-2 (Teodorczyk-Injeyan et al 1986, Sparkes 1993, Horgan et al 1994b. Thus it appears that the lack of IL-2, not IL-2R, is the critical defect in lymphocyte function after burn.…”

Section: Discussionmentioning

confidence: 99%

“…It has been well established that one of the main factors contributing to decreased T lymphocyte function, and thus cellular immunity, after burn injury is a dramatic decline in IL-2 production (Wolfe et al 1982, Wood et al 1984, Horgan et al 1994a, b, O'Riordain et al 1995. Clinically, the ability of peripheral blood mononuclear cells to produce IL-2 in vitro is positively correlated with survival after burn injury (Teodorczyk-Injeyan et al 1986, Sparkes 1993. In addition to the production and secretion of IL-2, T lymphocyte function is also dependent on expression of functional IL-2 receptor (IL-2R) on the cell surface.…”

Section: Introductionmentioning

confidence: 99%

“…There is conflicting evidence regarding the effect of burn injury on the expression of the IL-2R (Teodorczyk-Injeyan et al 1987, Horgan et al 1994a, O'Riordain et al 1995, Meert et al 1996. However, in studies in which the IL-2R was decreased after burn, inability to recover receptor expression was correlated with mortality after injury (Teodorczyk-Injeyan et al 1986, Sparkes 1993.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Testosterone receptor blockade restores cellular immunity in male mice after burn injury

Messingham¹,

Shirazi²,

Duffner³

et al. 2001

Journal of Endocrinology

View full text Add to dashboard Cite

Males are known to have increased risk for septic complications after traumatic injury, which appears to be mediated by the inhibitory effects of testosterone on immune function. The role of testosterone in immunity after burn injury, however, remains unclear. Herein, we examined the effects of a testosterone receptor antagonist, flutamide, on delayed type hypersensitivity response (DTH), splenocyte proliferation, interleukin (IL)-2 secretion, and IL-2 receptor (IL-2R) expression in male BALB/c mice subjected to a 15% total body surface area burn or sham injury. Burn-or sham-injured mice were given flutamide s.c. at 30 min and 24 h after injury. At 48 h, burn injury caused a 48% (P<0·001) decrease in DTH response; however, mice that received flutamide treatment did not demonstrate significant suppression of DTH. Likewise, splenocyte proliferation and IL-2 production were depressed in burned animals in comparison with sham-injured controls, and flutamide treatment resulted in a partial restoration of these responses. In vitro studies indicated that splenocytes from sham-and burninjured mice were equally sensitive to the suppressive effects of 5 -dihydrotestosterone in regard to proliferation and IL-2 production. Further evaluation revealed a decrease in IL-2R expression on splenocytes from burned mice and a partial restoration of this expression with flutamide treatment. Thus blocking testosterone receptor activation improves the cellular immunity in thermally injured mice, possibly through restoration of IL-2 production and IL-2R expression. It remains to be determined whether the effects of testosterone in this injury model are direct or indirect.

show abstract

Thermal injury-induced immunosuppression in mice: the role of macrophage-derived reactive nitrogen intermediates

Schwacha

Somers

1998

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Mechanisms of immune failure in burn injury

Cited by 30 publications

References 24 publications

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

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

Testosterone receptor blockade restores cellular immunity in male mice after burn injury

Thermal injury-induced immunosuppression in mice: the role of macrophage-derived reactive nitrogen intermediates

Contact Info

Product

Resources

About