1073 INTRAVENOUS HUMAN IMMUNE GLOBULIN PREVENTS NEUTRO PENIA, NEUTROPHIL SUPPLY EXHAUSTION AND DEATH IN EXPERIMENTAL GROUP B STREPTOCOCCAL SEPSIS

Abstract

In neonatal animals with group B streptococcal (GBS) sepsis, neutropenia and depletion of the marrow neutrophil (neut) reserves are prevented and survival markedly improved by murine hybridoma anti-GBS antibody. This product is not practical for use in human infants, however, because of its non-human origin. Therefore, we tested intravenous immune globulin (IVIG) for its effect on blood and marrow neut kinetics and survival. Groups of 15-30 neonatal rats were transthoracically inoculated with 10⁵ GBS/gm. All animals which received 40 ml/kg (containing 5 gm% IgG) lived (albumin control survival = 0%), 95% given 20 ml/kg survived, and 20% given 2 ml/kg lived. Even when delayed for 2h, 20 ml/kg resulted in 100% survival. Survival fell to 57% when IVIG was delayed for 6h and to 46% at 22h. IVIG also facilitated the neut inflammatory response: 1) IVIG recipients released neut more promptly from the marrow (after 2h, IVIG animals had released 5.5±0.8×10⁶ neut from reserves vs 1.2±0.6×10⁶ in controls, x±SEM, p<0.05), 2) IVIG prevented neutropenia (2763±216/mm³ IVIG vs 148±38/mm³ control, p<0.001), 3) neut supply did not become exhausted in IVIG recipients (4.5±0.5×10⁶ reserve neut 20h after inoculation vs 0.3±0.1×10⁶ in controls, p<0.001), 4) accumulation of neut at the site of GBS inoculation was more rapid (myeloper-oxidase-a neut marker-in lung 2h after inoculation=1.7±0.2 units vs 1.0±0.1 in controls, p<0.05). Therefore, IVIG markedly facilitated the neut response and improved survival. These findings provide support for a trial of IVIG in infected human neonates.

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