Group B streptococcus induces tumor necrosis factor in neonatal piglets. Effect of the tumor necrosis factor inhibitor pentoxifylline on hemodynamics and gas exchange.
Group B streptococcus (GBS), a common neonatal gram-positive pathogen, causes similar pathophysiologic features in human newborns and neonatal animal models of sepsis. Previous reports suggest that mediators in addition to TxA2 and PGI2 contribute to the late effects of GBS infusion (2 to 4 h), which include persistent increases in Ppa, hypoxemia, systemic hypotension, and a progressive fall in CO. Tumor necrosis factor (TNF) infusion in animals produces several of the late GBS effects. We hypothesized that GBS causes increased serum TNF levels 2 to 4 h into infusion in neonatal piglets. We also postulated that the TNF inhibitor, pentoxifylline (PTF), would attenuate both GBS-induced TNF production and late GBS effects. In piglets infused with 1.25 x 10(9) cfu/kg/h of GBS, serum TNF levels (pg/ml, ELISA assay) significantly increased at 2 h (231 +/- 41) and at 4 h (1,047 +/- 290, n = 9). In piglets infused with concomitant GBS + PTF, serum TNF levels at 4 h (208 +/- 39, n = 8) were reduced compared to GBS alone piglets (p less than 0.02). Control piglets infused with 0.9% saline or PTF alone for 4 h had no detectable serum TNF (less than 35). GBS alone and GBS + PTF infusion caused similar increases in serum TxB2 levels at 1, 2, and 4 h. Serum 6-keto-PGF1 alpha levels (pg/0.1 ml) significantly increased at 4 h (85 +/- 18) with GBS alone, and were more elevated at 4 h (306 +/- 75) with GBS + PTF infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Gibson
R L
RL
Department of Pediatrics, University of Washington School of Medicine, Seattle 98195.
Redding
G J
GJ
Henderson
W R
WR
Truog
W E
WE
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D000831:Animals, Newborn / Q000097:blood*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D010431:Pentoxifylline / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D013292:Streptococcus agalactiae / Q000502:physiology*; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014655:Vascular Resistance / Q000187:drug effects
D014409:Tumor Necrosis Factor-alpha; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D010431:Pentoxifylline