title: Detrimental role of CC chemokine receptor 4 in murine polymicrobial sepsis.
abstract: CC chemokine receptor 4 (CCR4) and its two ligands, CCL17 and CCL22, are critically involved in different immune processes. In models of lipopolysaccharide-induced shock, CCR4-deficient (CCR4(-/-)) mice showed improved survival rates associated with attenuated proinflammatory cytokine release. Using CCR4(-/-) mice with a C57BL/6 background, this study describes for the first time the role of CCR4 in a murine model of polymicrobial abdominal sepsis, the colon ascendens stent peritonitis (CASP). CASP-induced sepsis led to a massive downregulation of CCR4 in lymphoid and nonlymphoid tissues, whereas the expression of CCL17 and CCL22 was independent of the presence of CCR4. After CASP, CCR4(-/-) animals showed a strongly enhanced bacterial clearance in several organs but not in the peritoneal lavage fluid and the blood. In addition, significantly reduced levels of proinflammatory cytokines/chemokines were measured in organ supernatants as well as in the sera of CCR4(-/-) mice. CCR4 deficiency consequently resulted in an attenuated severity of systemic sepsis and a strongly improved survival rate after CASP or CASP with intervention. Thus, our data provide clear evidence that CCR4 plays a strictly detrimental role in the course of polymicrobial sepsis.
authors.affiliation: Department of Surgery, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany. traeger@uni-greifswald.de
authors.forename: Tobias
authors.initials: T
authors.lastname: Traeger
authors.forename: Wolfram
authors.initials: W
authors.lastname: Kessler
authors.forename: Volker
authors.initials: V
authors.lastname: Assfalg
authors.forename: Katharina
authors.initials: K
authors.lastname: Cziupka
authors.forename: Pia
authors.initials: P
authors.lastname: Koerner
authors.forename: Constanze
authors.initials: C
authors.lastname: Dassow
authors.forename: Katrin
authors.initials: K
authors.lastname: Breitbach
authors.forename: Marlene
authors.initials: M
authors.lastname: Mikulcak
authors.forename: Ivo
authors.initials: I
authors.lastname: Steinmetz
authors.forename: Klaus
authors.initials: K
authors.lastname: Pfeffer
authors.forename: Claus-Dieter
authors.initials: CD
authors.lastname: Heidecke
authors.forename: Stefan
authors.initials: S
authors.lastname: Maier