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PubMed2006

ENU-mutagenesis: insight into immune function and pathology.

In random chemical mutagenesis, gene discovery is driven by phenotypes rather than by hypotheses. A standard dose of N-ethyl-N-nitrosourea results in approximately 30 coding mutations in male G1 mice, of which approximately 4 can be propagated to homozygosity in 3 generations. In recent years, large-scale screens of such G3 mice for phenotypes of interest to immunologists have revealed clues to the number of genes responsible for key immune responses, such as innate recognition of pathogens and autoantibody production. More than 20 of the phenotypes that exhibit a simple (Mendelian) pattern of inheritance have been mapped. Novel alleles have revealed new pathways of host defense, allergy and autoimmunity.

Alleles↗
PubMed1982

Assessment of immune function development in mice irradiated in utero with 2450-MHz microwaves.

Groups of time-bred pregnant mice were irradiated with 2450-MHz microwaves at an incident power density of 28 mW/cm2 for 100 min daily from day 6 to day 18 of pregnancy. The average specific absorption rate (SAR) was 16.5 W/kg. Two experiments were performed under these conditions. At 3 and 6 weeks of age the mice were assessed for development of the primary immune response to sheep erythrocytes, in vitro mitogen-stimulated lymphocyte proliferation, and natural killer (NK) cell activity. No consistent significant difference in the primary immune response, in the mitogen response, or in the NK cell activity was observed between irradiated and sham-irradiated mice.

Animals↗
PubMed2005

Immune function biomarkers in children exposed to lead and organochlorine compounds: a cross-sectional study.

BACKGROUND: Different organochlorines and lead (Pb) have been shown to have immunomodulating properties. Children are at greater risk for exposure to these environmental toxicants, but very little data exist on simultaneous exposures to these substances. METHODS: We investigated whether the organochlorine compounds (OC) dichlorodiphenylethylene (DDE), hexachlorobenzene (HCB), hexachlorocyclohexane (gamma-HCH), the sum of polychlorinated biphenyls (SigmaPCBs) and Pb were associated with immune markers such as immunoglobulin (Ig) levels, white blood cell (WBC), counts of lymphocytes; eosinophils and their eosinophilic granula as well as IgE count on basophils. The investigation was part of a cross-sectional environmental study in Hesse, Germany. In 1995, exposure to OC and Pb were determined, questionnaire data collected and immune markers quantified in 331 children. For the analyses, exposure (OC and Pb) concentrations were grouped in quartiles (gamma-HCH into tertiles). Using linear regression, controlling for age, gender, passive smoking, serum lipids, and infections in the previous 12 months, we assessed the association between exposures and immune markers. Adjusted geometric means are provided for the different exposure levels. RESULTS: Geometric means were: DDE 0.32 microg/L, SigmaPCBs 0.50 microg/L, HCB 0.22 microg/L, gamma-HCH 0.02 microg/L and Pb 26.8 microg/L. The SigmaPCBs was significantly associated with increased IgM levels, whereas HCB was inversely related to IgM. There was a higher number of NK cells (CD56+) with increased gamma-HCH concentrations. At higher lead concentrations we saw increased IgE levels. DDE showed the most associations with significant increases in WBC count, in IgE count on basophils, IgE, IgG, and IgA levels. DDE was also found to significantly decrease eosinophilic granula content. CONCLUSION: Low-level exposures to OC and lead (Pb) in children may have immunomodulating effects. The increased IgE levels, IgE count on basophils, and the reduction of eosinophilic granula at higher DDE concentrations showed a most consistent pattern, which could be of clinical importance in the etiology of allergic diseases.

B-Lymphocytes↗
PubMed1986

Regulation of guinea-pig immune functions by interleukin 2: critical role of natural killer activity in acute HSV-2 genital infection.

We have previously demonstrated that recombinant interleukin 2 (rIL 2) has a protective effect against acute HSV-2 infection in guinea pigs with a biphasic dose response which peaked between 4 and 20 X 10(4) U/kg, whereas 8 X 10(5) U/kg showed no effect on disease. Animals that escaped infection appeared lack immunologic memory to HSV-2, suggesting a nonspecific immune mechanism. In this study we have found that NK activity of fresh splenocytes measured against HSV-2 infected human foreskin fibroblast (HFF) is stimulated in vitro and in vivo by rIL 2 in a biphasic dose range similar to that determined for protection against disease. In contrast, lymphokine-activated killer (LAK)-mediated lysis of P815 showed a linear response to increasing concentrations of rIL 2 both in vitro and in vivo. Transfer of LAK cells did not alter the rate of infection after HSV-2 challenge. Anti-asialo GM-1 eliminated rIL 2 protection against HSV-2 infection. It also blocked HSV-2/HFF lysis and partially decreased P815 lysis in vitro; however, in vivo it inhibited both natural killer (NK) activity and LAK generation, failing to distinguish which of the lytic cells was responsible for the effect against infection. Early IgG production (7 days post-infection) was enhanced by rIL 2 administration before viral inoculation, but it did not influence the rate of infection as compared with controls. Polyclonal IgM secretion was not found to play a role in acute protection. Circulating serum interferon levels were enhanced with increasing concentrations of rIL 2 but did not correlate with the biphasic dose curve for protection. Therefore of these mechanisms the one that is most closely related to the protective effect of rIL 2 against primary HSV-2 infection appears to be NK-mediated lysis, although the other mechanisms may add to this effect.

Animals↗
PubMed1984

The role of rabbit Ia molecules in immune functions as determined with the use of an anti-Ia monoclonal antibody.

We have produced a mouse anti-rabbit Ia monoclonal antibody (MAb) that detects an isotypic determinant on all rabbit Ia molecules. This MAb precipitates three polypeptide chains with molecular weights of 28,000, 31,000 and 35,000, corresponding to the Ia beta, Ii and alpha chains, respectively. The anti-Ia MAb inhibits the mixed lymphocyte culture by 80%. In secondary in vitro immune response cultures, the anti-Ia MAb inhibits the proliferative response to bovine insulin and poly (Glu50Tyr50). In studies on mitogenesis it was found that the anti-Ia MAb inhibited the response to LPS but not to concanavalin A or phytohaemagglutinin. The effect of the anti-Ia MAb on other mitogens was found to vary from rabbit to rabbit.

Animals↗
PubMed1993

Effects of voluntary exercise on immune function in rats.

We investigated effects of voluntary wheel running on specific antibody responses to Keyhole Limpet Hemocyanin (KLH) and on mitogen-stimulated lymphocyte proliferation in adult male rats. Each subject was placed in a running wheel for 12 h daily during the dark portion of the light cycle for a total of 8 weeks. For experimental animals the wheels rotated freely, enabling subjects to exercise at will, while for control animals the wheels were prevented from rotating. Subjects were immunized with KLH (25 micrograms) 5 weeks into the study, and blood samples were collected intermittently from the tail for 3 weeks and later assayed for anti-KLH antibody levels. At the end of the study, subjects were sacrificed and spleens were dissected and assayed for lymphocyte proliferative responses to the mitogen Concanavalin A. Exercised rats gained less weight and had higher splenic proliferative responses than control rats; however, there were no significant group differences in anti-KLH antibody levels.

Animals↗
PubMed1987

Ultraviolet-A light prolongs survival and improves immune function in (New Zealand black x New Zealand white)F1 hybrid mice.

Although ultraviolet (UV) light is generally harmful to patients with systemic lupus erythematosus, most clinical and immunologic studies of UV exposure have evaluated the effects of UV-B (280-320 nm). The long-wavelength UV-A band (320-400 nm), however, is less toxic than UV-B and has different immunologic actions. Therefore, we studied the effect of UV-A irradiation on survival and immunologic function in the (New Zealand black x New Zealand white)F1 hybrid mouse model of systemic lupus erythematosus. Twenty-one (New Zealand black x New Zealand white)F1 mice were treated with 3.5 joules/cm2/day of UV-A light for 5 days each week, beginning at age 10 weeks. A control group consisted of 20 untreated animals. All UV-A-irradiated mice survived to 32 weeks, compared with 12 of 20 mice in the nonirradiated group (P = 0.0013). Splenomegaly was significantly decreased in the irradiated mice (P less than 0.03). Mice that received UV-A treatment combined with depilation had significantly improved lymphocyte responses to phytohemagglutinin and lipopolysaccharide and significantly decreased levels of anti-DNA antibodies compared with mice that received neither treatment. Reductions in spleen size and anti-DNA antibody titer were significantly correlated with improved parameters of lymphocyte function. These results suggest that a relatively small dose of UV-A exerts significant therapeutic action in murine lupus, perhaps through an effect on immunologic regulation.

Animals↗
PubMed1990

Anabolic steroid effects on immune function: differences between analogues.

As an untoward effect of chronic anabolic steroid use, immunologic alterations may be induced. To evaluate this possibility five commercially available steroids with various types of structural differences were studied in male Sprague-Dawley rats. Animals were divided into five groups and treated with testosterone (Group 1), testosterone propionate (Group 2), testolactone (Group 3), oxandrolone (Group 4), and stanozolol (Group 5). Androgenic anabolic steroids were administered daily, subcutaneously dissolved in oil, at a dose of 1.1 mg/kg. Immune alterations were assessed by skin-test responses to phytohemagglutinin. After five days of treatment (1.1 mg/kg/day) a significant immuno-suppression was observed with all groups. However, by day 10, groups 3, 4, and 5 showed an immuno-stimulation. Using oxandrolone as the model stimulant, serum testosterone levels were significantly suppressed, while castration abolished the stimulatory effect. These observations indicate that immune alterations do occur with anabolic steroids which are immuno-suppressive when the steroid nucleus is intact and immuno-stimulatory with nuclear alterations. It appears that these changes are associated with altered gonadal testosterone release.

Anabolic Agents↗
PubMed2004

Physiological difference between free and triglyceride-type conjugated linoleic acid on the immune function of C57BL/6N mice.

Previous studies have shown the physiological significance of dietary conjugated linoleic acid (CLA) in various experimental animals and in human beings. One of the important problems to better elucidate is the difference between triglyceride (TG) and free (FFA) dietary CLA. Here, using splenocytes, this study assesses how TG- and FFA-CLA modulate immunoglobulin and various cytokine productions. In this study, C57BL/6N mice were fed an experimental diet containing 0% CLA, 0.1 or 1% FFA-CLA, or 0.1 or 1% TG-CLA for 3 weeks. The production of immunoglobulin tended to be up-regulated by 1% FFA-CLA. As a result of protein array analysis using the supernatant from splenocytes cultured with no CLA, 1% FFA-CLA, and TG-CLA, some cytokine production was shown to be remarkably regulated by dietary FFA- and TG-CLA. A total of 32 cytokines were examined, and 11-14 produced cytokines that were 2-fold up-regulated as compared with control for FFA- or TG-CLA, respectively. Especially, the production of IL-9 and MCP-5 and other cytokines was remarkably up-regulated by both FFA- and TG-CLA. In addition, seven cytokines were 2-fold down-regulated by TG-CLA. These data show that there is a slight but significant difference between the functionalities of FFA- and TG-CLA.

Animals↗
PubMed1983

The effects of ketoconazole on cellular and humoral immune functions.

The effects of ketoconazole at varying concentrations on in-vitro neutrophil random migration, chemotaxis to autologous endotoxin--activated serum and the synthetic chemotactic tripeptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine, phagocytosis and postphagocytic hexose monophosphate shunt activity and myeloperoxidase--mediated protein iodination were investigated. Neutrophil functions, in-vivo mitogen-induced lymphocyte transformation and levels of serum immunoglobulins and complement components were also assessed before and after ingestion of ketoconazole by six individuals. It was found that ketoconazole caused stimulation of neutrophil migration to leucoattractants 2 h after ingestion of a single dose of 400 mg ketoconazole. This stimulation was not sustained. The drug had no effect on the random migration of neutrophils. Likewise serum levels of the immunoglobulins IgG, IgM and IgA, total haemolytic complement and serum levels of the complement components C3 and C4 were unaffected. Ketoconazole in vitro had no effect on the neutrophil functions tested. Ingestion of ketoconazole caused a slight inhibition of lymphocyte mitogen-induced transformation.

Adult↗
PubMed1993

Does supplemental arginine alter immune function following major surgery?

Provision to surgical patients of parenteral arginine with minimal additional calories did not enhance proliferation of mononuclear cells. Earlier reports of the immunostimulatory effects of arginine may reflect interactions between arginine and other dietary components rather than exclusive effects of supplemental arginine.

Aged↗
PubMed1999

Altered immune function in human newborns after prenatal administration of betamethasone: enhanced natural killer cell activity and decreased T cell proliferation in cord blood.

During the course of human pregnancy, glucocorticoid (GC) treatment is given when preterm delivery is expected. This treatment is successful in stimulating the development of the fetal lung. However, in animal studies, a number of side effects of perinatal GC treatment have been described. The aim of the present study was to evaluate in humans the effects of antenatal GC treatment on development of the immune system. In addition, we examined the development of immune reactivity in infants born preterm and at term who did not receive GC treatment antenatally. We tested mitogen-induced T cell proliferation, natural killer cell activity, and lipopolysaccharide-induced IL-6 production in cord blood samples. We found that there is a significant effect of gestational age on the capacity of T cells to proliferate and of natural killer cells to kill K562 tumor cells. The capacity to produce IL-6 does not change between gestational age 26 and 41 wk. Moreover, our results show that antenatal treatment with GC does have immunomodulatory effects: T cell proliferation is decreased in infants born very preterm (gestational age 26-31 wk) as well as in infants born between 32 and 36 wk of gestation. In contrast, the activity of natural killer cells is only increased in GC-treated infants born between 26 and 31 wk. We did not observe a significant effect of antenatal GC treatment on the capacity to produce IL-6.

Betamethasone↗
PubMed1996

Dietary Spirulina platensis enhances humoral and cell-mediated immune functions in chickens.

Cornell K-strain White Leghorns and broiler chicks were raised to 7 wks and 3 wks of age respectively, with diets containing various levels (0, 10, 100, 1,000 and 10,000 ppm) of Spirulina platensis from day of hatch. Chicks in all treatment groups had comparable body weights. While bursal and splenic weights did not change, the K-strain chicks had larger thymuses (P < or = .05) over the controls (0 ppm group). No differences were observed in anti-sheep red blood cells antibodies during primary response. However, during secondary response, K-strain chicks in all Spirulina-dietary groups had higher total anti-SRBC titers with 10,000 ppm group being the highest (6.8 Log2) versus the 0 ppm (5.5 Log2) group. In broiler chicks, a one Log increase in IgG (P < or = .05) was observed in 10,000 ppm group over the controls. Similarly, chicks in 10,000 ppm Spirulina group had a higher PHA-P-mediated lymphoproliferative response over the 0 ppm controls. Macrophages isolated from both K-strain (10,000 ppm group) and broilers from all Spirulina groups had higher phagocytic potential than the 0 ppm groups. Spirulina supplementation at 10,000 ppm level also increased NK-cell activity by two fold over the controls. These studies show that Spirulina supplementation increases several immunological functions implying that a dietary inclusion of Spirulina at a level of 10,000 ppm may enhance disease resistance potential in chickens.

Adjuvants, Immunologic↗