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During this immunosuppressive phase, patients may have difficulty eradicating invading pathogens and are susceptible to life\u2010threatening secondary hospital\u2010acquired infections. Due to progress in antimicrobial treatment and supportive care, most patients survive early sepsis. Mortality is more frequently attributed to subsequent secondary nosocomial infections and multiorgan system failure. 6\u2010Gingerol is the major pharmacologically active component of ginger. Although it is known to exhibit a variety of biological activities, including anti\u2010inflammation and antioxidation, the role of 6\u2010gingerol in sepsis\u2010induced immune dysfunction remains elusive. Thus, we investigated whether 6\u2010gingerol improves septic host response to infections during sepsis. 6\u2010Gingerol\u2010treated mice showed significantly lower mortality in polymicrobial sepsis induced by cecal ligation and puncture LPS via enhanced bacterial clearance in the peritoneum, blood, and organs (liver, spleen, and kidney) and inhibited the production of TNF\u2010<jats:italic>\u03b1<\/jats:italic> and IL\u20106 in TLR2 and\/or TLR4\u2010stimulated macrophages. In addition, we demonstrated that survival improvement of secondary infection following septic insult was associated with an initial response of enhanced neutrophil numbers and function at the infection site, reduced apoptosis of immune cells, and a shift from a T helper cell type 2 (Th2) to a T helper cell type 1 (Th1) cytokine balance in the hypoinflammation phase. Our overall findings suggest that 6\u2010gingerol potentially restores sepsis\u2010induced immune dysfunction by shifting the balance of Th1\/Th2 and by regulating apoptosis of immune cells.<\/jats:p>","DOI":"10.1155\/2021\/5427153","type":"journal-article","created":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T02:20:33Z","timestamp":1640830833000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Pretreatment with 6\u2010Gingerol Ameliorates Sepsis\u2010Induced Immune Dysfunction by Regulating the Cytokine Balance and Reducing Lymphocyte Apoptosis"],"prefix":"10.1155","volume":"2021","author":[{"given":"Seong-A","family":"Ju","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quang-Tam","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thu-Ha T.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Hee","family":"Suh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won G.","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zak","family":"Callaway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeonsoo","family":"Joe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4802-7467","authenticated-orcid":false,"given":"Hun Taeg","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5176-0881","authenticated-orcid":false,"given":"Byung-Sam","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,29]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060872"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra021333"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3552"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03530120060042"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-018-0821-8"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2007.03.010"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.shk.0000191414.94461.7e"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0105017"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2009.10.004"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/biof.78"},{"key":"e_1_2_10_11_2","first-page":"S36","article-title":"Anti-oxidative and anti-inflammatory effects of ginger in health and physical activity: review of current evidence","volume":"4","author":"Mashhadi N. 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