Plasma Cytokines After Thermal Injury and Their Relationship to Infection

Drost, Adriana; Burleson, David G.; Cioffi, William G.; Mason, Arthur D.; Pruitt, Basil A.

doi:10.1097/00000658-199307000-00012

Cited by 126 publications

(41 citation statements)

References 12 publications

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“…Burn injury appears to prime macrophages to subsequent stimulation as evidenced by increased production of inflammatory mediators such as TNF-␣, IL-6, nitric oxide, and PGE 2 [7][8][9]. Macrophage hyperactivity, defined as the increased productive capacity for inflammatory mediators, has been implicated in the increased susceptibility to sepsis after thermal injury.…”

Section: Discussionmentioning

confidence: 99%

“…This immune dysfunction following thermal injury appears to involve multiple factors, including T lymphocyte dysfunction [4,5], increased levels of Th-2 cytokines [i.e., interleukin (IL)-4, IL-10] [6], and increased production of macrophage inflammatory mediators [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

“…Thermal injury appears to prime macrophages to subsequent stimuli as evidenced by enhanced in vitro production of inflammatory mediators [22,23]. Moreover, systemic levels of these mediators are elevated post-burn [8]. Macrophage hyperactivity, i.e., the increased production of inflammatory mediators such as TNF-␣ has been implicated in the increased susceptibility to sepsis after thermal injury [7,9,24].…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…Data from clinical studies as well as animal models of trauma and sepsis have shown that elevations in IL-6 production can be directly correlated with suppressed cellular immune responses and overall poor clinical prognosis [8][9][10]. Several different cell types are capable of producing IL-6, including fibroblasts, lymphocytes, and cells of the monocyte/ macrophage lineage.…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoids protect against suppression of T cell responses in a murine model of acute ethanol exposure and thermal injury by regulating IL-6

Faunce

Gregory

Kovacs

1998

Journal of Leukocyte Biology

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Previous reports by this laboratory demonstrated that acute alcohol exposure combined with a 15% body surface area dorsal scald injury results in significant reductions in delayed-type hypersensitivity (DTH) and splenocyte proliferative responses compared to either insult alone. Previous studies by this lab have also shown that these defects are mediated, in part, by increased production of interleukin-6 (IL-6). Because both alcohol exposure and thermal injury are known to modulate glucocorticoid (CORT) levels, and CORT regulates IL-6 gene expression, the relationship between circulating CORT and IL-6 production in burn ؉ ethanol mice was examined . At 24 and 48 h post-burn, a positive correlation existed between circulating CORT levels and measurements of cellular immune function. Administration of exogenous CORT to burn ؉ ethanol-treated mice resulted in significant restoration (to 60% of control) of DTH and splenocyte proliferative responses. This restoration was concomitant with a down-regulation of circulating and macrophage-derived IL-6. The specificity of CORT in modulating these responses was tested by assessing cellular immune function and IL-6 levels after glucocorticoid receptor blockade with RU486. Taken together, these data strongly suggest that under normal circumstances CORT protects burned mice from severe immune dysfunction, a protection that is not afforded to burn ؉ ethanol-treated mice. Furthermore, the immune dysfunction observed in burn ؉ ethanol mice may be due to a lack of glucocorticoid attenuation of IL-6. J. Leukoc. Biol. 64: 724-732; 1998.

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“…Associam-se, especialmente nos casos graves, a APR, com os conseqüentes aumentos de níveis circulantes de citocinas, como a IL-6 e o TNF-α 49 . A IL-2 tem seus níveis reduzidos 50 .…”

Section: Resposta Ao Trauma E Cirurgiaunclassified

Resposta celular ao estresse

Meyer¹,

Silva²

1999

Rev. Assoc. Med. Bras.

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Nos últimos dez anos, mais de 10.000 trabalhos científicos foram publicados a respeito das HSP (Heat Shock Proteins), ou proteínas do choque térmico, e da resposta ao choque térmico, ou HSR (Heat Shock Response). Muitos outros vieram à luz focalizando outras respostas celulares ao estresse. O conhecimento destes fenômenos básicos é indispensável à compreensão de inúmeras condições patológicas. As aplicações clínicas são potencialmente muito vastas e podem vir a ser fundamentais em diversas doenças, hoje de difícil abordagem, como a síndrome de resposta inflamatória sistêmica, o câncer, as doenças infecciosas e outras. Múltiplas pesquisas estão em andamento, há ainda muito o que se descobrir, mas a relevância do assunto justifica plenamente o seu estudo e a sua divulgação. Resposta ao choque térmico (HSR -Heat Shock Response)Em 1962, descobriu-se que a exposição de célu-las de glândulas salivares de Drosophila busckii a calor, dinitrofenol ou salicilatos 2 produzia o surgimento, em cromossomos, de um novo padrão de espessamento, que representava sítios específicos de transcrição para a síntese de proteínas. O estresse térmico ou químico induzia a expressão de genes, até então quiescentes, os quais faziam com que as células estressadas fabricassem grande quantidade de uma determinada classe de proteí-nas, que foram chamadas de Heat Shock Proteins (HSP), ou proteínas do choque térmico. O processo pelo qual as células respondiam ao estresse ficou conhecido como Heat Shock Response (HSR), ou resposta ao choque térmico.Verificou-se, posteriormente, que a HSR era um fenômeno praticamente universal entre todos os seres vivos 3 . Esta resposta é caracterizada por um aumento extremamente rápido na expressão de um grupo seleto de proteínas, as HSP, o que não ocorre apenas após exposição ao calor, mas também quando as células são expostas a diversos outros desafios metabólicos, incluindo análogos de aminoácidos, diversos metais pesados, agentes que modificam as sulfidrilas protéicas, diversos ionóforos e outros venenos metabólicos 4 . Os agentes anti-reumáticos à base de sais de ouro,como auro-tiomalato de sódio e auranofim, foram capazes de induzir a expressão de HSP em macrófagos murinos cultivados 5 .As HSP são uma classe de proteínas altamente conservadas, desde seres primitivos (procariotas) até o homem, o que é um indício de seu grande valor evolutivo 6 . As HSP podem ser agrupadas em famílias: HSP-27, HSP-47, HSP-60, HSP-70, HSP-90 e HSP-110 3 , de acordo com suas seqüências de aminoácidos e com seus pesos moleculares (em kD -quilodaltons), determinados pelo método SDS-PAGE (eletroforese em gel de poliacrilamidasódio-dodecil-sulfato) 7 . Em cada família, há diferentes proteínas -por exemplo, HSP-72 e HSP-73 no grupo HSP-70; os pesos moleculares são similares, mas os padrões de indução e expressão são distintos. A família HSP-70 é a mais conservada filogeneticamente; sua estrutura, no homem, é 72% homóloga em relação às HSP-70 de drosófilas 8 . As famílias HSP-60 e HSP-70 são as mais ligadas ao processo geral de dobra...

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Plasma Cytokines After Thermal Injury and Their Relationship to Infection

Abstract: These results suggest that IL6 and TNF alpha play a role in the response of burned patients to infection.

Cited by 126 publications

References 12 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

Glucocorticoids protect against suppression of T cell responses in a murine model of acute ethanol exposure and thermal injury by regulating IL-6

Resposta celular ao estresse

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