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However, the involvement of peripheral cytokines synthesized during systemic inflammation as modulators of the tonic immobility (<jats:styled-content style=\"fixed-case\">TI<\/jats:styled-content>) defensive behaviour remains a literature gap. Our purposes were to characterize the <jats:styled-content style=\"fixed-case\">TI<\/jats:styled-content> defensive behaviour in endotoxemia guinea\u2010pigs at acute phase and after recovery from the initial inflammatory challenge. Furthermore, we investigated whether peri\u2010aqueductal grey matter (<jats:styled-content style=\"fixed-case\">PAG<\/jats:styled-content>) exists as a brain structure related to this behaviour and also pro\u2010inflammatory cytokines, tumour necrosis factor (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>)\u2010<jats:italic>\u03b1<\/jats:italic> and interleukin (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>)\u20101<jats:italic>\u03b2<\/jats:italic>, act at this mesencephalic nucleus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Endotoxemia was induced by lipopolysaccharide (<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>) administration in guinea\u2010pigs. The parameters evaluated included <jats:styled-content style=\"fixed-case\">TI<\/jats:styled-content> defensive behaviour, survival, cytokines production, as well as neuronal activation and apoptosis in the <jats:styled-content style=\"fixed-case\">PAG<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Endotoxemia guinea\u2010pigs exhibited a reduction in the duration of <jats:styled-content style=\"fixed-case\">TI<\/jats:styled-content> episodes, starting at 2\u00a0h after <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> administration and persisting throughout the experimental period evaluated over 7\u00a0days. Moreover, endotoxemia increased the c\u2010<jats:styled-content style=\"fixed-case\">FOS<\/jats:styled-content> immunoreactivity of neurones in the ventrolateral <jats:styled-content style=\"fixed-case\">PAG<\/jats:styled-content> (vl<jats:styled-content style=\"fixed-case\">PAG<\/jats:styled-content>), as well as the caspase\u20103 expression. The <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> microinjection into vl<jats:styled-content style=\"fixed-case\">PAG<\/jats:styled-content> reproduces the same compromise, that is a decrease in the duration of <jats:styled-content style=\"fixed-case\">TI<\/jats:styled-content> defensive behaviour, observed after the peripheral administration. The immunoneutralization against <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101<jats:italic>\u03b2<\/jats:italic> and <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010<jats:italic>\u03b1<\/jats:italic> into vl<jats:styled-content style=\"fixed-case\">PAG<\/jats:styled-content> reverts all the effects produced by peripheral <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings confirm that vl<jats:styled-content style=\"fixed-case\">PAG<\/jats:styled-content> is an important brain structure involved in the behavioural alterations induced by endotoxemia, possibly changing the neuronal activity caused by pro\u2010inflammatory cytokines produced peripherally.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.12729","type":"journal-article","created":{"date-parts":[[2016,6,4]],"date-time":"2016-06-04T06:42:50Z","timestamp":1465022570000},"page":"123-135","source":"Crossref","is-referenced-by-count":9,"title":["Pro\u2010inflammatory cytokines, <scp>IL<\/scp>\u20101<i>\u03b2<\/i> and <scp>TNF<\/scp>\u2010<i>\u03b1<\/i>, produce persistent compromise in tonic immobility defensive behaviour in endotoxemia guinea\u2010pigs"],"prefix":"10.1111","volume":"218","author":[{"given":"A. 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