Psychological variables as predictors of rubella antibody titers and fatigue--a prospective, double blind study.

When exposed to infectious pathogens, human beings manifest variability in the incidence and severity of infection. This variability may partly depend on psychological variables, which have long been thought to contribute to the predisposition, onset, and course of various physical illnesses, including infectious diseases. The objective of the study was to investigate the predictive value of several personality and other psychological variables on antibody titers and fatigue following a specific viral infection. Subjects were divided into a seronegative group (not immune prior to vaccination) (N = 60) and a seropositive group (immune prior to vaccination) (N = 180), based on antibody titers to rubella before and 10.5 weeks after vaccination with live-attenuated rubella virus. Questionnaires assessing externalizing, internalizing, self-esteem, neuroticism, and fatigue-related symptoms were administered to the subjects before vaccination. Fatigue-related symptoms were re-evaluated 10 weeks post vaccination. In the seronegative group, low titers of rubella antibodies, 10.5 post-vaccination, were predicted by high internalizing or neuroticism scores, and by low self-esteem, measured at baseline. Higher externalizing scores indirectly predicted lower titers of antibodies, via fatigue-related symptoms, measured 10 weeks post vaccination. In contrast, in the seropositive group no association was found between any of the psychological variables and antibody titers. Personality and other psychological variables can predict antibody titers to rubella vaccination, in infected individuals. The associations between the psychological variables and antibody titers are complex, and involve both direct and indirect associations. Specific psychological variables can also be used to predict levels of post-vaccination fatigue.

Fetal alcohol exposure attenuates interleukin-1beta-induced fever: neuroimmune mechanisms.

Central mechanisms for the attenuating effects of fetal alcohol exposure (FAE) on interleukin-1beta (IL-1beta)-induced fever were studied in adult male offspring of dams fed a liquid diet supplemented with ethanol (E), in pair-fed (P) control and in normal (N) offspring. Hypothalamic levels of IL-1 were significantly lower in E than in N rats at 2 h, but not at 4 and 6 h, after intraperitoneal administration of lipopolysaccharide. Fever induced by intracerebroventricular (i.c.v.) IL-1 was significantly lower in E than in N and P rats. In contrast, E rats showed a normal febrile response to i.c.v. prostaglandin-E2. Thus, whereas FAE does not affect central thermoregulatory mechanisms, per se, FAE alters the kinetics of hypothalamic IL-1 production/appearance and decreases the responsiveness of central mechanisms which mediate the febrile response to IL-1.

Cytokines inhibit sexual behavior in female rats: II. Prostaglandins mediate the suppressive effects of interleukin-1beta.

The proinflammatory cytokine interleukin-1 (IL-1) induces several behavioral alterations that are characteristic of illness, such as anorexia and reduced locomotor and social activity. We have recently demonstrated that IL-1 inhibits sexual activity, motivation and attractivity in female, but not in male rats following either central or peripheral administration. In the present study we examined the involvement of prostaglandin (PG) synthesis in mediating IL-1-induced suppression of female sexual behavior. Administration of the cyclooxygenase blockers indomethacin or ibuprofen completely prevented IL-1-induced suppression of female sexual behavior, including the reduction in proceptive behavior, the lordosis response to a male's mounts, and the preference for a sexually active partner. In a subsequent study, ex-vivo release of hypothalamic PGE2 and the secretion of corticosterone (CS) were measured in males and estrous females following IL-1 administration. At the same time and dose of IL-1 administration that significantly reduced sexual behavior in female but not male rats, IL-1 produced a significant increase in PGE2 release in female, but not in male rats. In contrast, IL-1 induced a significant elevation of serum CS levels in males but not in females. These findings suggest that PG synthesis is involved in mediating the effects of IL-1 on female sexual behavior. Furthermore, differential secretion of PGs and CS may underlie the gender difference in the effects of IL-1 on sexual behavior.

Influence of socioeconomic status on behavioral, emotional and cognitive effects of rubella vaccination: a prospective, double blind study.

A double-blind prospective design was used to investigate the immediate and prolonged psychological effects of a specific viral infection, and the role of immune activation in mediating these effects. Subjects were 240 female teenager girls who were vaccinated with rubella vaccine. Based on analysis of levels of antibodies to rubella, subjects were divided into two groups. An experimental group (n = 60), which included subjects who were initially seronegative and were infected following vaccination, and a control group (n = 180), which included subjects who were already immune to rubella before vaccination. Compared with the control group and to their own baseline, low socioeconomic status (SES) subjects within the experimental group showed a significant increase in the severity of depressed mood, social and attention problems, and delinquent behavior. Ten weeks post-vaccination there were no differences between the experimental and control groups in serum levels of interleukin-1 beta, interferon-gamma, soluble interleukin-2 receptors (sIL-2r), and cortisol. However, a significant negative correlation was found between fatigue-related symptoms and sIL-2r levels in the experimental (r = -0.325), but not the control group (r = -0.046). These findings suggest that viral infection can produce prolonged behavioral, emotional and cognitive problems mainly in subjects belonging to the low SES.

Effects of bacterial endotoxin on the glucocorticoid feedback regulation of adrenocortical response to stress.

Previous studies have shown that LPS and cytokines modulate the binding of glucocorticoids (GCs) in the CNS, and therefore may affect the negative feedback exerted by GCs. In this study, we investigated the effect of lipopolysaccharide (LPS) on the inhibitory action of GCs upon the adrenocortical response to a neural stressful stimulus. Male rats were treated with either LPS (50 micrograms/kg) or saline for 5 consecutive days. Two days later, the LPS- and saline-treated rats were injected intraperitoneally with either dexamethasone (20 micrograms/kg) or saline and sacrificed 3.5 h later, after exposure to acute stressful photic stimulation. In saline-pretreated rats, photic stimulation caused a 5-fold increase in serum corticosterone levels compared to basal levels, and pretreatment with dexamethasone completely abolished this response. In LPS-pretreated rats, corticosterone levels following photic stimulation increased 20-fold, and dexamethasone was ineffective. Additional experiments were conducted to examine whether the impairment in the negative feedback was specific to the prolonged LPS treatment, rather than to LPS-induced hypersecretion of GCs. In groups of rats which were exposed to either daily acoustic stress or daily administration of corticosterone (5 mg, twice daily) for 5 days, the pattern of corticosterone secretion mimicked the corticosterone secretion induced by LPS. In these groups, the adrenocortical response to acute photic stimulation and the effect of dexamethasone were similar to saline-pretreated controls. These results suggest that LPS impairs the negative feedback of either endogenous or exogenous GC upon the adrenocortical response to stress. This finding may be relevant to the enhanced adrenocortical activity associated with sepsis and major depression.

Salt preference in rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain).

Brattleboro rats are homozygous for diabetes insipidus (HO-DI), lacking the ability to synthesize vasopressin. Besides increasing water consumption, HO-DI rats may compensate for their excessive renal water loss by reducing their intake of and preference for substances that elevate plasma osmolarity. In two experiments we assessed this possibility. In Experiment 1, salt preference of HO-DI and control Long-Evans (LE) rats was measured by presenting the rats with two tubes: one filled with water and the other with NaCl. In the first part of the experiment, 18 NaCl concentrations were presented in increasing order (from 6 to 300 mM). In the second part, other groups of HO-DI and LE rats were presented with 6 concentrations of NaCl, ranging from 6 to 450 mM in either increasing or decreasing order of concentrations. In Experiment 2, preference for 6 concentrations of citric acid ranging from 0.1 to 6 mM was assessed. With NaCl concentrations greater than 100 mM, intake and preference declined rapidly for the HO-DI group but very gradually for the LE group. In contrast, the HO-DI rats preferred all citric acid solutions more than LE rats. The results suggest that HO-DI rats compensate for their inability to concentrate urine not only by increasing water consumption, but also by decreasing consumption of and preference for salty solutions.