A hypothesis consistent with the known facts is that endotoxin appearing in the circulating plasma by direct leakage from the gut or derived from endotoxin producing bacteria translocated from the gut in response to injury is the trigger for the abnormalities of cellular immunity noted after major burns or serious injury. We propose to test this hypothesis by studying patients who have sustained major burns or traumatic injury and a mouse model of burn injury in order to correlate serum endotoxin levels with cytokine production by adherent cells, lymphocytes and PMN and with cytokine messenger RNA expression by the same cells. We will also correlate adherent cell PGE2 production with lymphocyte activation and cytokine production. We will investigate inhibitors of the arachadonic acid pathway on the expression of messenger RNA for IL-2 and interferon gamma. We will also investigate second messenger activity in lymphocytes by measuring by cyclic AMP levels and will investigate the mechanism of increased sensitivity of lymphocytes to PGE2 after injury by exposing normal lymphocytes to cytokines, cortisol and PGE2. Finally we will utilize the animal model of burn injury to determine whether immunoregulatory regimens which increase survival after septic challenge will increase splenocyte IL-2 production and/or diminish splenocyte proinflammatory cytokine production.
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| Osuka, Akinori; Hanschen, Marc; Stoecklein, Veit et al. (2012) A protective role for inflammasome activation following injury. Shock 37:47-55 |
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| Hanschen, Marc; Tajima, Goro; O'Leary, Fionnuala et al. (2011) Injury induces early activation of T-cell receptor signaling pathways in CD4+ regulatory T cells. Shock 35:252-7 |
| O'Leary, Fionnuala M; Tajima, Goro; Delisle, Adam J et al. (2011) Injury-induced GR-1+ macrophage expansion and activation occurs independently of CD4 T-cell influence. Shock 36:162-9 |
| Fujimi, Satoshi; Lapchak, Peter H; Zang, Yan et al. (2009) Murine dendritic cell antigen-presenting cell function is not altered by burn injury. J Leukoc Biol 85:862-70 |
| Maung, Adrian A; Fujimi, Satoshi; MacConmara, Malcolm P et al. (2008) Injury enhances resistance to Escherichia coli infection by boosting innate immune system function. J Immunol 180:2450-8 |
| Purcell, Elizabeth M; Dolan, Sinead M; Kriynovich, Sara et al. (2006) Burn injury induces an early activation response by lymph node CD4+ T cells. Shock 25:135-40 |
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