title: Plasma cytokine profiles in preprotachykinin-A knockout mice subjected to polymicrobial sepsis.
abstract: During the course of polymicrobial sepsis, a range of pro- and antiinflammatory cytokines are produced by the host immune system. Successful recovery from sepsis involves striking a balance between these counteracting cytokines. We herein investigated the circulating cytokine profiles in preprotachykinin-A knockout (PPTA(-/-)) mice, which have been found to be protected significantly against microbial sepsis, by employing multiplexed bead-based suspension arrays for the measurement of 18 plasma cytokines. Four sets of PPTA(-/-) and wild-type mice, each with six mice, were subjected to cecal ligation and puncture-induced sepsis or a sham procedure and were killed at 1, 5, 8 and 24 h post surgery. The cytokine profiles revealed, rather interestingly, that both pro- and antiinflammatory cytokines were elevated in the knockout group in response to a septic challenge. The higher systemic levels of both pro- and antiinflammatory cytokines in PPTA(-/-) septic mice was similar to the increase that we observed earlier in lung tissue of PPTA(-/-) mice after induction of sepsis. Thus, elevated levels of both pro- and antiinflammatory mediators may act simultaneously and help to resolve the infectious assault at the early stages of sepsis without excessively damaging the host tissue in PPTA(-/-) mice. In addition, our results underline the importance of comprehensive clinical analysis of multiple biomarkers to provide a better prognostic tool.
authors.affiliation: Cardiovascular Biology Program, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Akhil
authors.initials: A
authors.lastname: Hegde
authors.forename: Mahesh
authors.initials: M
authors.lastname: Uttamchandani
authors.forename: Shabbir M
authors.initials: SM
authors.lastname: Moochhala
authors.forename: Madhav
authors.initials: M
authors.lastname: Bhatia
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002432:Cecum / Q000601:surgery; D016207:Cytokines / Q000097:blood* / Q000276:immunology; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011498:Protein Precursors / Q000235:genetics* / Q000276:immunology; D018805:Sepsis / Q000097:blood* / Q000235:genetics / Q000276:immunology; D015320:Tachykinins / Q000235:genetics* / Q000276:immunology
chemical_list: D016207:Cytokines; D011498:Protein Precursors; D015320:Tachykinins; C044206:preprotachykinin