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With the pathophysiology of sepsis remaining largely unknown, the uncontrolled reactive oxygen species (ROS) production along with the decreased antioxidants contributes to the progression toward septic shock. Being the effector cells of the innate immunity system, macrophages secrete both pro\u2010inflammatory and anti\u2010inflammatory mediators during inflammation. Lipopolysaccharide (LPS) binding to toll\u2010like receptor 4 (TLR4) releases TNF\u2010\u03b1, which initiates pro\u2010inflammatory events through tumor necrosis factor receptor 1 (TNFR1) signaling. However, it is counteracted by the anti\u2010inflammatory interleukin 10 (IL\u201010) causing decreased oxidative stress. Our study thus aimed to assess the effects of exogenous IL\u201010 treatment post\u2010neutralization of TLR4 and TNFR1 (by anti\u2010TLR4 antibody and anti\u2010TNFR1 antibody, respectively) in an in vivo murine model of LPS\u2010sepsis. We have also examined the tissue\u2010specific antioxidant status in the spleen, liver, and lungs along with the serum cytokine levels in adult male Swiss albino mice to determine the functional association with the disease. The results showed that administration of recombinant IL\u201010 post\u2010neutralization of the receptors was beneficial in shifting the macrophage polarization to the anti\u2010inflammatory M2 phenotype. IL\u201010 treatment significantly downregulated the free radicals production resulting in diminished lipid peroxidase (LPO) levels. The increased antioxidant activities of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR<jats:sub>X<\/jats:sub>) conferred protection against LPS\u2010induced sepsis. Western blot data further confirmed diminished expressions of TLR4 and TNFR1 along with suppressed stress\u2010activated protein kinases\/Jun amino\u2010terminal kinases (SAPK\/JNK) and increased SOD and CAT expressions, which altogether indicated that neutralization of TLR4 and TNFR1 along with IL\u201010 posttreatment might be a potential therapeutic measure for the treatment of sepsis.<\/jats:p>","DOI":"10.1002\/jat.4496","type":"journal-article","created":{"date-parts":[[2023,5,13]],"date-time":"2023-05-13T02:13:30Z","timestamp":1683944010000},"page":"1549-1572","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Exogenous IL\u201010 posttreatment along with TLR4 and TNFR1 blockade improves tissue antioxidant status by modulating sepsis\u2010induced macrophage polarization"],"prefix":"10.1002","volume":"43","author":[{"given":"Ritasha","family":"Sawoo","sequence":"first","affiliation":[{"name":"Department of Physiology, Immunology Laboratory University of Calcutta, University Colleges of Science and Technology  Calcutta India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajen","family":"Dey","sequence":"additional","affiliation":[{"name":"Department of Physiology, Immunology Laboratory University of Calcutta, University Colleges of Science and Technology  Calcutta India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rituparna","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Physiology, Immunology Laboratory University of Calcutta, University Colleges of Science and Technology  Calcutta India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8603-8621","authenticated-orcid":false,"given":"Biswadev","family":"Bishayi","sequence":"additional","affiliation":[{"name":"Department of Physiology, Immunology Laboratory University of Calcutta, University Colleges of Science and Technology  Calcutta India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1974.tb03751.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2007.08.006"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.5339\/qmj.2020.22"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2018.07.003"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1995-7645(13)60183-2"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.5152\/TJAR.2014.83436"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.174.6.1549"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.09.004"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.10.010"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0076-6879(78)52032-6"},{"issue":"4","key":"e_1_2_9_12_1","first-page":"629","article-title":"Organ dysfunction in sepsis: An ominous trajectory from infection to death","volume":"92","author":"Caraballo C.","year":"2019","journal-title":"The Yale Journal of Biology and Medicine"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-016-0640-8"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40560-017-0243-y"},{"issue":"6","key":"e_1_2_9_15_1","first-page":"669","article-title":"Role of cytokines as a double\u2010edged sword in sepsis","volume":"27","author":"Chaudhry H.","year":"2013","journal-title":"In Vivo (Athens, Greece)"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107791"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753425916668243"},{"issue":"5","key":"e_1_2_9_18_1","first-page":"361","article-title":"Rapid determination of urea nitrogen in serum or plasma without deproteinization","volume":"33","author":"Crocker C. 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