Interleukin-4 Treatment Restores Cellular Immunity After Ethanol Exposure and Burn Injury

Messingham, Kelly A. N.; Heinrich, Scott A.; Schilling, Eric M.; Kovacs, Elizabeth J.

doi:10.1097/00000374-200204000-00013

Cited by 3 publications

(3 citation statements)

References 62 publications

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“…However, a shift in the cytokine response from Th1 to Th2 cannot always be used as a general indicator of immune status after injury, as our laboratory has previously reported immune de- fects that appear later (7-10 days) after injury in the presence of high levels of IFN-␥ [4]. Additionally, using a murine model of burn injury combined with acute ethanol exposure, we observed that IL-4 levels were actually suppressed and that administration of IL-4 to achieve levels similar to sham-injured mice actually restored immunity [43]. It should be noted, however, that the cytokines reported in those studies were induced by pan stimulation of T cells rather than via Agspecific pathways.…”

Section: Discussionsupporting

confidence: 53%

A role for CD1d-restricted NKT cells in injury-associated T cell suppression

Faunce

Gamelli

Choudhry

et al. 2003

Journal of Leukocyte Biology

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Natural killer T (NKT) cells are known to modulate T cell responses during autoimmunity, tolerance, and antitumor immunity; however, their potential role in regulating the immune response to injury has not been reported. Using a murine model of burn injury, we investigated whether CD1d-restricted NKT cells played a role in the T cell suppression that occurs early after injury. A functional role for CD1d stimulation of NKT cells in the injury-related immune suppression was demonstrated by experiments in which the suppression of antigen (Ag)-specific delayed-type hypersensitivity and in vitro T cell-proliferative responses were prevented if mice were given anti-CD1d monoclonal antibody (mAb) systemically just before injury. The CD1d-NKT cell-dependent suppression of the T cell response after injury occurred in the absence of quantitative changes in NKT cells themselves or CD1d(+) Ag-presenting cells. We observed that elevated production of the immunosuppressive cytokine interleukin (IL)-4 correlated with burn-induced immune dysfunction, and we found that NKT cells but not conventional T cells were the source of IL-4 early after injury. Lastly, we observed that the injury-induced production of NKT cell-derived IL-4 could be blocked by systemic treatment of burn-injured mice with anti-CD1d mAb. Together, our results reveal a novel mechanism involving CD1d stimulation of NKT cells in the onset of T cell suppression that occurs subsequent to injury.

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Section: Discussionsupporting

confidence: 53%

A role for CD1d-restricted NKT cells in injury-associated T cell suppression

Faunce

Gamelli

Choudhry

et al. 2003

Journal of Leukocyte Biology

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“…This study also confirmed that increased levels of CECs correspond to increased levels of proinflammatory cytokines in the acute phase of burn and inhalation injury in relation to the severity of injury and as the patients develop complications or die. As noted in the literature, there was an elevation in plasma levels of IL-10 26,27 and IL-4, 28 anti-inflammatory cytokines, with the increase in the proinflammatory cytokines. As reported by Yeh et al, 29 IL-10 levels were decreased in survivors compared with nonsurvivors.…”

Section: Discussionsupporting

confidence: 58%

Circulating Endothelial Cell Levels Correlate with Proinflammatory Cytokine Increase in the Acute Phase of Thermal Injury

Kowal-Vern¹,

Webster²,

Rasmasubban³

et al. 2005

Journal of Burn Care & Rehabilitation

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Circulating endothelial cells (CECs) are increased in sickle cell disease, myocardial infarction, and acute lung injury. The purpose of this study was to determine whether CECs are a prognosticating marker for the development of pneumonia in burn patients with/without inhalation injury in addition to their relationship to proinflammatory cytokines. There were 24 patients: 6 with inhalation injury, 5 with burn only,and 13 with burn plus inhalation injury. CECs were measured by anchored cytometry (Clarient ChromaVision, San Juan Capistrano, CA). In addition, plasma levels of tumor necrosis factor-alpha, interferon-gamma, and interleukins (IL)-10, IL-6, IL-4, and IL-2 were compared with CEC levels. Patients with inhalation injury had a significant (P < .001) paucity of CECs compared with the thermally injured with inhalation. There was a statistically significant increase in inteferon-gamma, tumor necrosis factor-alpha, and IL-6, IL-4, and IL-2 compared with control patients (P < .01), with a concomitant increase in the number of CECs. The numbers of CEC levels did not prognosticate which patients would develop pneumonia. Burn patients with/without inhalation injury had concurrent increase in CECs and proinflammatory cytokines during the acute phase of injury.

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“…Although the overall impact of EtOH intoxication on postburn pathogenesis remains to be investigated, a few studies have suggested that the patients who consumed EtOH before injury are more susceptible to infection, exhibit higher morbidity, and are more likely to die than patients who have not consumed EtOH (18,(33)(34)(35)54). Similarly, findings from experimental settings suggest that EtOH intoxication before burn injury exacerbates the suppression of host immune defense, deteriorates intestinal barrier functions, and increases intestinal bacterial translocation (4,6,13,26,28,35,36).…”

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confidence: 99%

Acute alcohol intoxication increases interleukin-18-mediated neutrophil infiltration and lung inflammation following burn injury in rats

Kovacs

Schwacha

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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In this study, we examined whether IL-18 plays a role in lung inflammation following alcohol (EtOH) and burn injury. Male rats ( approximately 250 g) were gavaged with EtOH to achieve a blood EtOH level of approximately 100 mg/dl before burn or sham injury ( approximately 12.5% total body surface area). Immediately after injury, rats were treated with vehicle, caspase-1 inhibitor AC-YVAD-CHO to block IL-18 production or with IL-18 neutralizing anti-IL-18 antibodies. In another group, rats were treated with anti-neutrophil antiserum approximately 16 h before injury to deplete neutrophils. On day 1 after injury, lung tissue IL-18, neutrophil chemokines (CINC-1/CINC-3), ICAM-1, neutrophil infiltration, MPO activity, and water content (i.e., edema) were significantly increased in rats receiving a combined insult of EtOH and burn injury compared with rats receiving either EtOH intoxication or burn injury alone. Treatment of rats with caspase-1 inhibitor prevented the increase in lung tissue IL-18, CINC-1, CINC-3, ICAM-1, MPO activity, and edema following EtOH and burn injury. The increase in lung IL-18, MPO, and edema was also prevented in rats treated with anti-IL-18 antibodies. Furthermore, administration of anti-neutrophil antiserum also attenuated the increase in lung MPO activity and edema, but did not prevent the increase in IL-18 levels following EtOH and burn injury. These findings suggest that acute EtOH intoxication before burn injury upregulates IL-18, which in turn contributes to increased neutrophil infiltration. Furthermore, the presence of neutrophils appears to be critical for IL-18-meditaed increased lung tissue edema following a combined insult of EtOH and burn injury.

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Interleukin-4 Treatment Restores Cellular Immunity After Ethanol Exposure and Burn Injury

Cited by 3 publications

References 62 publications

A role for CD1d-restricted NKT cells in injury-associated T cell suppression

A role for CD1d-restricted NKT cells in injury-associated T cell suppression

Circulating Endothelial Cell Levels Correlate with Proinflammatory Cytokine Increase in the Acute Phase of Thermal Injury

Acute alcohol intoxication increases interleukin-18-mediated neutrophil infiltration and lung inflammation following burn injury in rats

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