Protection against lethal intra-abdominal sepsis by 1-(3-dimethylaminopropyl)-3-ethylurea.
Sodium hyaluronate-carboxymethylcellulose (HA/CMC) formulations are gels that effectively reduce postoperative adhesions in both animals and humans, when placed in the peritoneal or pelvic cavities concomitant with surgical manipulation. However, it has been suggested that the use of these products may increase the risk of peritoneal infection after contamination with intestinal contents during surgery. Using the rat intra-abdominal sepsis model, we found that administration of HA/CMC gels before bacterial challenge did not increase mortality but did significantly protect rats against lethal infection. This effect was dose and time dependent. Protection was conferred not by the HA/CMC gels themselves but by 1-(3-dimethylaminopropyl)-3-ethylurea (EDU), a small molecule released from the gel complex under physiologic conditions. Our results suggest that the protective effect exhibited by EDU is related to down-regulation of T cell-dependent responses and suppression of the proinflammatory-cytokine cascade associated with mortality during the early phase of disease.
Ruiz-Perez
Begoña
B
Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. bruiz@rics.bwh.harvard.edu.
Cisneros
Ronald L
RL
Matsumoto
Tetsuya
T
Miller
Robert J
RJ
Vasios
George
G
Calias
Pericles
P
Onderdonk
Andrew B
AB
D018784:Abdominal Abscess / Q000517:prevention & control*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004927:Escherichia coli Infections / Q000517:prevention & control*; D005782:Gels / Q000737:chemistry / Q000494:pharmacology*; D006820:Hyaluronic Acid / Q000737:chemistry; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000517:prevention & control*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*
C477080:1-(3-dimethylaminopropyl)-3-ethylurea; D000276:Adjuvants, Immunologic; D016207:Cytokines; D005782:Gels; D014508:Urea; D006820:Hyaluronic Acid; D002266:Carboxymethylcellulose Sodium