title: Impact of prostaglandin and thromboxane synthesis blockade on disposition of group B streptococcus in lung and liver of intact piglet.
abstract: Group B streptococci (GBS) localizing in the lungs of infant piglets is killed in part by an oxygen radical-dependent mechanism (Bowdy BD, Marple SL, Pauly TH, Coonrod JD, Gillespie MN: Am Rev Respir Dis 141:648-653, 1990). The source of bactericidal oxygen radicals is unknown, but cyclooxygenation of arachidonic acid, an initial event in prostanoid synthesis, is accompanied by substantial oxygen radical generation. Because blockade of prostaglandin H synthase (cyclooxygenase) with indomethacin prevents GBS-induced pulmonary hypertension, we reasoned that the salutary effect of indomethacin might be associated with a reduction in the efficacy of bactericidal activity directed against GBS. To address this possibility, the distribution and viability of 111In-labeled GBS (10(8) colony forming units/kg/min i.v. for 15 min) were assessed in lungs and livers of control piglets, piglets treated with indomethacin (1 mg/kg), and piglets treated with OKY-046 (10 mg/kg), an inhibitor of thromboxane synthase that also forestalls GBS-induced pulmonary hypertension. Relative to control animals, indomethacin treatment increased pulmonary GBS uptake with no change in bacterial distribution into the liver. OKY-046 failed to influence pulmonary bacterial uptake but promoted a substantial increase in GBS depositing in the liver. In contrast to its effects on pulmonary bacterial deposition, indomethacin failed to increase lung bacterial viability relative to control animals. Indomethacin also was without effect on hepatic bacterial viability. OKY-046 failed to influence pulmonary bacterial viability but markedly augmented hepatic GBS viability to the extent that significant bacterial proliferation occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pediatrics, College of Medicine, University of Kentucky A. B. Chandler Medical Center, Lexington 40536-0082.
authors.forename: T H
authors.initials: TH
authors.lastname: Pauly
authors.forename: S M
authors.initials: SM
authors.lastname: Aziz
authors.forename: S J
authors.initials: SJ
authors.lastname: Horstman
authors.forename: M N
authors.initials: MN
authors.lastname: Gillespie
mesh_terms: D000818:Animals; D005609:Free Radicals; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000517:prevention & control; D007213:Indomethacin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D008689:Methacrylates / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D013290:Streptococcal Infections / Q000150:complications; D013292:Streptococcus agalactiae / Q000302:isolation & purification*; D013552:Swine; D013931:Thromboxanes / Q000096:biosynthesis
chemical_list: D005609:Free Radicals; D008689:Methacrylates; D011453:Prostaglandins; D013931:Thromboxanes; C034364:ozagrel; D007213:Indomethacin