title: Effect of CL 184,005, a platelet-activating factor antagonist in a murine model of Staphylococcus aureus-induced gram-positive sepsis.
abstract: Experiments using a murine model of heat-killed Staphylococcus aureus-induced gram-positive bacterial sepsis indicate that the lethal bacterial effects can be prevented if mice are pretreated with CL 184,005, a platelet-activating factor (PAF) antagonist. CL 184,005 was ineffective when administered after bacterial challenge. Plasma of mice pretreated with CL 184,005 contained significantly less tumor necrosis factor (TNF), suggesting that CL 184,005 interferes with TNF synthesis induced by S. aureus. Spleen-associated TNF protein was also decreased by pretreatment with CL 184,005. Although TNF levels were significantly decreased in mice treated with CL 184,005, interleukin-6 levels in serum were significantly increased. Athymic mice were also susceptible to the lethal effects of S. aureus, suggesting that T cells were not involved. When rats rendered hypotensive with S. aureus were treated with CL 184,005, their blood pressure was normalized. Mice treated with enterotoxin B were not protected if they were pretreated with CL 184,005; however, TNF levels in these mice were significantly lower, suggesting that mediators other than PAF and TNF may contribute to the lethal effects of enterotoxin.
authors.affiliation: Oncology and Immunology Research Section, American Cyanamid Company, Lederle Laboratories, Pearl River, New York 10965.
authors.forename: S Q
authors.initials: SQ
authors.lastname: DeJoy
authors.forename: R
authors.initials: R
authors.lastname: Jeyaseelan
authors.forename: L W
authors.initials: LW
authors.lastname: Torley
authors.forename: W C
authors.initials: WC
authors.lastname: Pickett
authors.forename: A
authors.initials: A
authors.lastname: Wissner
authors.forename: M M
authors.initials: MM
authors.lastname: Wick
authors.forename: A L
authors.initials: AL
authors.lastname: Oronsky
authors.forename: S S
authors.initials: SS
authors.lastname: Kerwar
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004768:Enterotoxins / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009943:Organophosphorus Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000209:etiology; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D004768:Enterotoxins; D015850:Interleukin-6; D009943:Organophosphorus Compounds; D010972:Platelet Activating Factor; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; C077460:CL 184005; C031818:enterotoxin B, staphylococcal