Seasonal immune function and sickness responses.
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We describe veno-occlusive disease of the liver associated with humoral and cellular immune defects in two siblings. Another child, with aplastic anemia, died before the age of 1 year. No consanguinity was found in the family. Both infants had lymphopenia and hypogammaglobulinemia; the surviving infant has defective in vitro immunoglobulin production after stimulation of lymphocytes with pokeweed mitogen, increased proportions of OKT8 positive cells, defective proliferative responses to phytomitogens, and decreased help for immunoglobulin production. A therapeutic trial with cimetidine, an H2 receptor antagonist, has not changed the immunologic status of the surviving child.
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Besides being a potent chemical carcinogen, benzo[a]pyrene (BaP) has also been shown to suppress the immune response of mammals. However, even though BaP is a ubiquitous environmental contaminant to which aquatic species may be directly exposed, information regarding the effects of BaP on the immune system of fish is still lacking. Therefore, laboratory studies were conducted using Japanese medaka (Oryzias latipes) to examine the effects of BaP on host immune status. A single IP injection of BaP at 2, 20 or 200 microg/g BW had no effect upon medaka survival or condition factors for up to 7 days post-injection. Forty-eight hours after injection of either BaP or the vehicle control, fish were sacrificed and the appropriate organs/cells used to assess effects upon: splenic lymphocyte proliferation; kidney phagocyte intracellular superoxide (*O(2)(-)) production; and, CYP1A protein level/activity. In separate experiments, fish were injected with either sheep red blood cells or the bacterial pathogen Yersinia ruckeri at 48 h post-BaP exposure for later determination of antibody-forming cell (AFC) numbers and bacterial host resistance, respectively. Results demonstrated that in the absence of effects upon host survival or condition factors, a single exposure to a relatively low dose of BaP (2 microg/g BW) significantly suppressed mitogen-stimulated T- and B-lymphocyte proliferation (in the absence of elevated hepatic CYP1A expression/activity). At higher concentrations, BaP also reduced AFC numbers, phagocyte-mediated *O(2)(-) production, and host resistance against bacterial infection. These results clearly demonstrate the ability of BaP to compromise the immune response of fish and indicate the utility of the fish immune response to serve as an early indicator of BaP exposure/effects in exposed feral populations.
It was postulated that frequent pulses of cortisol such as might be induced by a repeated or chronic stressor, could induce immune suppression and that the effect would be greater than in animals subjected to less frequent increases. Four groups of nine adult Scottish Blackface ewes were infused for 14 d with saline or hydrocortisone hemisuccinate (cortisol) delivered continuously or in pulses. Plasma concentrations of cortisol were significantly elevated (to between approximately 100 and 1000 nmol/liter; P < 0.001) for about 30 or 75 min after infusion of pulses of hydrocortisone hemisuccinate at intervals of 1 hr (P1) or 6 hr (P6), respectively. In animals continuously infused (CI), they were consistently elevated (P < 0.001), compared with concentrations in control animals infused with saline only (S), to approximately 1000 nmol/liter or more. Antibody production in response to ovalbumin injection was not affected by any of the infusion regimes. At Days 10, 24, and 31 after injection of ovalbumin and initiation of the infusion, rates of multiplication of unstimulated lymphocytes, in vitro, were greater (P < 0.05) in P6 animals than in saline-infused, control animals and this resulted in a reduction in the stimulated lymphocyte response. As a consequence of the increased basal lymphocyte activity, after Day 0, the corrected, stimulated lymphocyte response of P6 animals was consistently below that of controls (P < 0.05 at Day 24). Both mean basal and stimulated lymphocyte activities in CI and P1 animals were similar to those of controls. The gamma interferon (IFN-gamma) response was generally small and not affected by treatment. It is concluded that large, relatively infrequent increases in circulating cortisol concentrations can modify the cell mediated immune response such that the response to a specific antigen challenge is compromised but smaller, more frequent pulses had no effect. Elevated cortisol concentrations per se did not have a significant inhibitory effect on the immune system.
OBJECTIVE: To determine the effects of dietary consumption of Bifidobacterium lactis (strain HN019, DR10TM) on natural immunity. DESIGN: A randomized, double blind, placebo-controlled clinical trial. SETTING: Janeway Medical Centre, Memorial University, St Johns, Newfoundland. SUBJECTS: Twenty-five healthy elderly volunteers (median age 69 y; range 60-83 y). INTERVENTIONS: Twelve control subjects consumed 180 ml low-fat/low-lactose milk twice daily for a period of 6 weeks; 13 test subjects consumed milk supplemented with 1.5x1011 colony-forming units of B. lactis twice daily. Indices of natural immunity, including interferon production, phagocytic capacity and phagocyte-mediated bactericidal activity, were determined via peripheral blood at 0, 3, 6 and 12 weeks post-trial commencement. RESULTS: Subjects who consumed milk containing B. lactis for 6 weeks produced significantly enhanced levels of interferon-alpha, upon stimulation of their peripheral blood mononuclear cells in culture, in comparison to the placebo control group who received milk alone. There were also significant increases in polymorphonuclear cell phagocytic capacity among test group subjects, following consumption of milk supplemented with B. lactis, while individuals who consumed B. lactis-supplemented milk or milk alone showed enhanced phagocyte-mediated bactericidal activity. CONCLUSIONS: The results demonstrate that dietary consumption of B. lactis HN019 can enhance natural immunity in healthy elderly subjects, and that a relatively short-term dietary regime (6 weeks) is sufficient to impart measurable improvements in immunity that may offer significant health benefits to consumers. SPONSORS: Financial support for this project was provided by the New Zealand Dairy Board.
For almost half a century, the mouse model of Listeria monocytogenes infection has been used to analyse both innate and adaptive components of immunity and to discover key immune genes. Vast accumulated knowledge about the disease in mice provides a unique framework for identifying and characterising immune molecules using a variety of experimental approaches. To illustrate the range of questions that can be addressed using modern genetics and genomics tools, the authors provide an overview of the analysis of components of immune signalling networks using the mouse model of L. monocytogenes infection.
OBJECTIVE: To examine the impact of and relationship between exposure to Hurricane Andrew, a severe stressor, posttraumatic stress symptoms and immune measures. METHODS: Blood draws and questionnaires were taken from community volunteer subjects living in the damaged neighborhoods between 1 and 4 months after the Hurricane. RESULTS: The sample exhibited high levels of posttraumatic stress symptoms by questionnaire (33% overall; 76% with at least one symptom cluster), and 44% scored in the high impact range on the Impact of Events (IES) scale. A substantial proportion of variance in posttraumatic stress symptoms could be accounted for by four hurricane experience variables (damage, loss, life threat, and injury), with perceived loss being the highest correlate. Of the five immune measures studied Natural Killer Cell Cytotoxicity (NKCC) was the only measure that was meaningfully related (negatively) to both damage and psychological variables (loss, intrusive thoughts, and posttraumatic stress disorder (PTSD). White blood cell counts (WBCs) were significantly positively related with the degree of loss and PTSD experienced. Both NKCC (lower) and WBC were significantly related to retrospective self-reported increase of somatic symptoms after the hurricane. Overall, the community sample was significantly lower in NKCC, CD4 and CD8 number, and higher in NK cell number compared to laboratory controls. Finally, evidence was found for new onset of sleep problems as a mediator of the posttraumatic symptom-NKCC relationship. CONCLUSIONS: Several immune measures differed from controls after Hurricane Andrew. Negative (intrusive) thoughts and PTSD were related to lower NKCC. Loss was a key correlate of both posttraumatic symptoms and immune (NKCC, WBC) measures.
OBJECTIVES: To determine whether lifelong exposure to dehydroepiandrosterone sulfate extends the lifespan or retards immune senescence in mice. DESIGN: Double-blind, placebo-controlled intervention trial. SETTING: A specific pathogen-free rodent vivarium. PARTICIPANTS: 120 mice bred as a cross between CB6F1 females and C3D2F1 males. INTERVENTION: DHEAS at 100 microg/mL in drinking water from weaning until death. MEASUREMENT: Age at death, cause of death, antibody production after erythrocyte immunization, and T cell subset profiles in peripheral blood at ages 8 and 18 months. RESULTS: DHEAS ingestion did not lead to a significant increase in mean or maximal longevity: the 95% confidence interval for DHEAS effect on mean lifespan ranged from +35 days to -80 days. There were no significant effects of DHEAS on incidence of lethal illnesses, except for a trend toward higher levels of mammary adenocarcinoma in DHEAS-treated females and mouse urinary syndrome in DHEAS-treated males. DHEAS treatment did not improve the ability of middle-aged mice to produce antibody to a foreign particulate antigen, and it did not alter the proportions of age-sensitive T cell subsets in middle-aged animals. CONCLUSION: Although differences among species in pharmacokinetics complicate interpretation of studies in which DHEA or DHEAS is administered to rodents, our data provide no support for the idea that chronic exposure to this steroid retards immune senescence or prevents late life illness.
Glioma patients receiving corticosteroids (16 mg/day betamethasone) were examined for evidence of immune cell dysfunction by using quantitative estimates of adenosine diphosphate (ADP)-ribosylation in peripheral mononuclear leukocytes as the physiological indicator. The duration of daily treatment with corticosteroids varied from 0 to 35 days at the time of collection of the blood samples. Even after adjustment for covariate factors such as age, sex, smoking habits, alcohol use, antiepileptic medications, and tumor grade, there still remained a highly significant dose-dependent inverse relationship between constitutive and hydrogen peroxide-induced mononuclear leukocyte ADP-ribosylation levels and the duration of corticosteroid treatment (beta coefficients -0.40 and -0.29, respectively; p less than 0.03). No other variable under consideration significantly influenced ADP-ribosylation levels after statistical adjustment. These data support a mutual interdependence of mononuclear leukocyte ADP-ribosylation and corticosteroid-induced immune cell dysfunction in vivo.
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The rosette rates of erythrocytes C3b receptor (C3bR) and immune complex (IC) in normal and high-risk pregnant women were measured. The results showed that the rate of C3bR in normal gravidae was significantly higher than that in patients with pregnancy induced hypertensive syndrome (P less than 0.05). The rosette rate of IC in cases of premature rupture of membranes was significantly higher than that in normal pregnant women (P less than 0.01). In this paper, the rosette rates of C3bR and IC in normal gravidae, puerperas, neonates and control adults were compared and discussed.
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