ONICGENY OF DEVELOPMENT OF PHA-INDUCED GAMMA INTERFERON (IFN) PRODUCTION BY LYMPHOCYTES OF NORMAL INFANTS AND CHILDREN

Abstract

The increased severity of infections in young infants may be due to immaturity of the neonatal immune system. Studies have shown that lymphocytes from 1-7 day old infants make normal adult levels of alpha IFN, but have impaired production of PHA-induced gamma IFN. This impairment has been shown to be primarily due to a functionally immature neonatal macrophage. Gamma IFN production is important in recovery from viral infections and can also be used as a marker of macrophage function in infants. To determine the ontogeny of gamma IFN production in vivo, we obtained blood from 40 healthy children (age 1 day to 12 yrs), and 13 adult controls. Whole blood (adjusted to 2×105 lymphs/ml) was incubated with PHA-A in RPMI for 48 hrs, and supernates assayed for IFN expressed in International Units (IU) by protection of WISH human aminon cells from encephalomyocarditis virus challenge. All adults (13) produced IFN geometric mean titer (GMT) 114 IU (range 25-756 IU). In comparison healthy infants ages 0-75 days exhibited markedly decreased gamma IFN with only 8/26 producing any detectable IFN (range 0-480 IU), GMT 2.75 IU (p<.01). Infants from 75-180 days of age produced gamma IFN at intermediate levels of 0-240 IU GMT=50 (N=6). Adult levels of gamma IFN were produced by 7/8 children ≥180 days old (180 days-12 yrs) levels 0-980 IU, GMT=177 IU (N=8). This impaired gamma IFN production in infants ≤2½ mos. of age may represent a functionally immature macrophage system and may help explain the increased morbidity and mortality from bacterial and virus infections (particularly herpes simplex virus) in young infants.