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Alcohol consumption leads to an exaggerated inflammatory response after burn injury. Elevated levels of interleukin-6 (IL-6) in patients are associated with increased morbidity and mortality after injury, and high systemic and pulmonary levels of IL-6 have been observed after the combined insult of ethanol exposure and burn injury. To further investigate the role of IL-6 in the pulmonary inflammatory response, we examined leukocyte infiltration and cytokine and chemokine production in the lungs of wild-type and IL-6 knockout mice given vehicle or ethanol (1.11 g/kg) and subjected to a sham or 15% total body surface area burn injury. Levels of neutrophil infiltration and neutrophil chemoattractants were increased to a similar extent in wild-type and IL-6 knockout mice 24 h after burn injury. When ethanol exposure preceded the burn injury, however, a further increase of these inflammatory markers was seen only in the wild-type mice. Additionally, signal transducer and activator of transcription-3 (STAT3) phosphorylation did not increase in response to ethanol exposure in the IL-6 knockout mice, in contrast to their wild-type counterparts. Visual and imaging analysis of alveolar wall thickness supported these findings and similar results were obtained by blocking IL-6 with antibody. Taken together, our data suggest a causal relationship between IL-6 and the excessive pulmonary inflammation observed after the combined insult of ethanol and burn injury. [ABSTRACT FROM AUTHOR]

Abstract: CD8+ T cells are important for resolution of HSV-2 lesions from the female genital epithelium. It is uncertain whether optimal clearance of viruses such as HSV-2 that cause a limited, non-systemic infection solely requires expression of effector functions by infiltrating CD8+ T lymphocytes, or if the clearance rate is reflective of the expression level of critical effector functions. To address this, CD8+ T cells from normal OT-I mice or OT-I mice deficient in IFNγ (IFNγ−/−) or the IFNγ receptor (IFNγR−/−) were activated in vitro in the presence of IFNγ or IL-4 to generate a series of effector populations (Tc1 and Tc2-like respectively) that secreted different levels of IFNγ and expressed different levels of HSV-specific cytolytic function. Compared with Tc1 cells, Tc2-like cells produced the type 2 cytokines IL-4 and IL-5, exhibited decreased IFNγ secretion, diminished proliferation in vitro, and decreased antigen-specific cytolysis in vivo. Clearance of an ovalbumin-expressing HSV-2 strain (HSV-2 tk− OVA) by adoptively transferred Tc2-like cells was delayed relative to Tc1 cell recipients. Because donor Tc2-like cells proliferated in vivo and infiltrated the infected genital epithelium similar to Tc1 cells, the diminished virus clearance by Tc2-like effector cells correlated with reduced expression of critical effector functions. Together, these results suggest that high level expression of protective T cell functions by effector T cells is necessary for optimal clearance of HSV-2 from the genital epithelium. These results have important implications for vaccines designed to elicit CD8+ T cells against viruses such as HSV-2 that infect the genital tract. [Copyright &y& Elsevier]

Abstract: This article highlights the research presented at the Alcohol and Trauma Satellite Symposium at the 30th Annual Meeting of the Shock Society. The satellite meeting was held on June 8 and 9 in Baltimore, MD. Its purpose was to discuss recent findings in the areas of alcohol and injury, including the effect of alcohol use on patients in the trauma unit of hospitals. The meeting consisted of three sessions, with plenary talks by invited speakers, short talks from selected abstracts, and a poster session. Participants presented data on the effects of alcohol on organ function, healing, and immune processes after a variety of injuries including burn, hemorrhagic shock, sepsis, and ischemia reperfusion. [Copyright &y& Elsevier]

Abstract: Interferon gamma (IFNγ) is important for immune resistance to herpes simplex virus (HSV) infection. To examine the influence of IFNγ on the development of HSV-specific immune responses and test for IFNγ-independent adaptive immune mechanisms of protection, IFNγ-deficient mice (IFNγ−/−) were immunized with thymidine kinase-deficient HSV-2 (HSV-2 333tk−). HSV-specific cellular and humoral responses were elicited in immunized IFNγ−/− mice resulting in increased resistance relative to non-immune C57BL/6J (B6) mice following challenge with fully virulent HSV-2. CD8+ T cells from IFNγ−/− mice displayed cytotoxic activity and secreted TNFα. HSV-specific CD4+ T cells from immunized IFNγ−/− mice secreted IL-4, TNFα, and IL-17, but unlike T cells from HSV-immune B6 mice, could not clear virus from genital tissue following adoptive transfer. HSV-immune IFNγ−/− mice produced predominantly IgG1 HSV-specific antibodies while immune B6 mice produced predominantly IgG2c antibodies. Transfer of equivalent amounts of HSV-specific antibodies from either strain to naïve mice imparted equivalent early resistance against infection of the genital epithelia. However, protection against neurological symptoms mediated by immune B6 antibodies was superior late in infection. Taken together, these results demonstrate that the limited resistance of HSV-immune IFNγ−/− mice to HSV-2 infection resulted from the action of HSV-specific Ab rather than IFNγ-independent effector functions of T cells. Further, protection against neurological manifestations of HSV-2 infection was superior in mice receiving Ab from immune B6 mice suggesting that Ab-mediated protective mechanisms involving IFNγ-induced IgG subclasses were more effective once virus had spread to neural tissues. [Copyright &y& Elsevier]

Abstract: On November 18, 2011, the 16th annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at Loyola University Medical Center in Maywood, Illinois. The focus of this year''s meeting was alcohol''s effect on epigenetic changes and possible outcomes induced by these changes. Two sessions, which consisted of talks from invited speakers as well as presentations of selected abstracts, were held in addition to a poster session. Participants presented information on alcohol-induced alterations in histone modifications and gene expression along with immunologic responses to alcohol. Speakers shared new research specifically on histone deacetylase enzyme expression and modifications due to alcohol and the downstream effect of these modifications may have on gene expression and tissue damage. Additional studies suggested that alcohol exacerbates inflammation when combined with other insults such as infection, trauma, inhalation injury, and disease. [Copyright &y& Elsevier]

The 15th annual meeting of the Alcohol and Immunology Research Interest Group was held on November 19, 2010, at Loyola University Medical Center in Maywood, IL. This year, the focus of the meeting was on alcohol's effect on the immune system in both clinical and experimental systems. The event consisted of three sessions, which featured plenary talks from invited speakers along with oral presentations from selected abstracts, in addition to a poster session. Participants presented a variety of information on ethanol-induced effects on infection susceptibility and resolution, oxidative stress, and organ inflammation. Specifically, speakers presented new insights on the mechanism of alcohol-mediated deleterious effects in the lung, liver, skin, and neuroendocrine system, as well as on immune cells in both in vivo and in vitro systems. Additional oral presentations suggested possible mechanisms of how alcohol-induced reactive oxygen species promote immune dysregulation both locally and systemically. [ABSTRACT FROM AUTHOR]

Abstract: The 15th annual meeting of the Alcohol and Immunology Research Interest Group was held on November 19, 2010, at Loyola University Medical Center in Maywood, IL. This year, the focus of the meeting was on alcohol’s effect on the immune system in both clinical and experimental systems. The event consisted of three sessions, which featured plenary talks from invited speakers along with oral presentations from selected abstracts, in addition to a poster session. Participants presented a variety of information on ethanol-induced effects on infection susceptibility and resolution, oxidative stress, and organ inflammation. Specifically, speakers presented new insights on the mechanism of alcohol-mediated deleterious effects in the lung, liver, skin, and neuroendocrine system, as well as on immune cells in both in vivo and in vitro systems. Additional oral presentations suggested possible mechanisms of how alcohol-induced reactive oxygen species promote immune dysregulation both locally and systemically. [Copyright &y& Elsevier]