Gestational exposure to loud noise alters the development and postnatal responsiveness of humoral and cellular components of the immune system in offspring.

Gestational exposure of the female to environmental toxins can alter immune function in the offspring. We have recently shown that prenatal maternal stress, that is, stress applied to or induced in the female during pregnancy, can also alter the development of humoral immunocompetence in the offspring and their hormonal and immunologic responses to postnatal stress. This report presents data from two experiments on the effects of prenatal exposure to loud noise-prenatal sound stress (PSS)-on the development and responsiveness of in vitro and in vivo humoral and cellular immune function in the offspring. Pregnant rats were exposed daily from Day 15 to Day 21 of gestation to an inescapable loud noise (an 85- to 90-decibel fire alarm bell) delivered randomly for 1 hr. In developing offspring, PSS produced age-dependent and mitogen-specific alterations in lymphoproliferative activity and reduced immunoglobulin G levels at Postnatal Day 21. Antibody titers to herpes simplex virus type 1 were also reduced. Exposure to loud noise before or after infection produced an additional reduction in titers in these offspring. Arthus skin reaction (AR) to old tuberculin was reduced by PSS. Combined prenatal/postnatal sound stress further reduced this response and the AR to bovine serum albumin (BSA). Delayed hypersensitivity reaction to BSA was reduced in PSS offspring; postnatal sound stress enhanced the reaction to both antigens, but only in males. Antibody titers to BSA were increased by PSS; adjuvant-induced inflammation was attenuated by postnatal sound stress. These data suggest that in utero exposure to loud noise, which can occur in the workplace, is toxic to the developing immune system.

Neurobehavioral and immunological effects of prenatal cocaine exposure in rat.

Time-pregnant Sprague-Dawley rats were injected subcutaneously with 20 mg/kg of cocaine HCl or 0.9% saline daily from gestation days 15 through 21. Maternal plasma levels of approximately 720 ng/ml of cocaine did not alter maternal weight gain during treatment, duration of pregnancy, any of the litter variables or several indices of maternal behavior. Offsprings' body weight from birth to 30 days of age and physical maturation were not generally affected by prenatal cocaine exposure. While the development of surface righting, cliff avoidance, and the startle response was accelerated in cocaine-exposed offspring, acquisition of a preference for a social odor was unaltered. Prenatal cocaine also attenuated the locomotor response of the offspring to d-amphetamine and cocaine at PND 15; at PND 30 both of these catecholaminergic agonists increased activity in prenatal saline and prenatal cocaine offspring. However, the difference in plasma levels of cocaine at PND 30 suggests a possible down-regulation of adrenergic receptors following prenatal cocaine exposure. Decreased thymus/body weight ratios and splenomegaly were observed in prenatal cocaine animals at 55 days of age. Although complete neutralization of herpes simplex virus-type 1 was not observed, sera from prenatal cocaine offspring showed an increased rate of appearance of cytopathic effect, while sera from animals given cocaine postnatally showed a reduction in the rate at which viral infectivity was expressed in culture. These results indicate that prenatal cocaine exposure can alter neurobehavioral ontogeny and humoral immune responsitivity in the offspring.

Interaction of rheumatoid factor with infectious herpes simplex virus-antibody complexes.

Rheumatoid factor, a human immunoglobulin of the IgM class, failed to attach to herpes simplex virus but did attach to infectious complexes composed of herpes simplex virus and antibody to herpes simplex virus. These newly formed complexes of infectious virus, antiviral antibody, and rheumatoid factor could be neutralized by complement or by antibody to human IgM. The ability of rheumatoid factor to enhance virus neutralization in the presence of complement represents a hitherto unrecognized biological role for rheumatoid factor.

Kinetics of sensitization of herpes simplex virus and its relationship to the reduction in the neutralization rate constant.

Incubation of herpes simplex virus (HSV) with rabbit anti-HSV for as little as 2.5 minutes rendered 75% of the surviving fraction neutralizable by anti-rabbit-gamma-globulin antiserum. The degree of this sensitization increased with time and at 20 minutes over 99.8% of the surviving virus was sensitized. Neutralization kinetics showed that as the degree of sensitization increased, the neutralization rate constant decreased. Incubation of HSV with anti-HSV for 5, 20, and 120 minutes resulted, respectively, in a 23%, 59%, and 87% reduction in the neutralization rate constant. These findings suggest that sensitization is an important factor in the inhibition of neutralization and the formation of the persistent fraction.