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 < 0.02). Control piglets infused with 0.9% saline or PTF alone for 4 h had no detectable serum TNF (< 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. PVR significantly increased at 1, 2, and 4 h with GBS alone; PVR was reduced (approximately 20%) at 1, 2, and 4 h with GBS+PTF compared with GBS alone infusion (p < 0.05). GBS+PTF piglets had significantly improved arterial PO2 values (mm Hg) at 4 h (72 +/- 2) compared with GBS alone piglets (59 +/- 3). GBS+PTF piglets showed greater systemic hypotension at 4 h compared with GBS alone piglets. We conclude that circulating TNF is a potential mediator of late GBS effects in neonatal piglets. PTF treatment attenuates GBS-induced TNF production and results in a mild improvement in pulmonary hemodynamics and hypoxemia in a piglet model of GBS sepsis.