Immune Function In Rats Research Articles

High Dietary Intakes of Vitamin E and Cellular Immune Functions in Rats

High dietary intakes (100-2500 mg/kg diet) of vitamin E (dl-alpha-tocopheryl acetate) modified the functions of splenic lymphocytes and alveolar macrophages (AM). The numbers of splenocytes and AM obtained from male F344 rats fed high vitamin E diets significantly increased at 10 d after the onset of the experiment. Splenic lymphocytes' responses to concanavalin A and natural killer cell activity also increased with increasing contents of vitamin E in the diets. Furthermore, the ability of AM to phagocytose opsonized sheep red blood cells increased with increasing contents of vitamin E in diets and showed a fivefold increase in rats fed the diet with the highest vitamin E content (2500 mg/kg diet) compared with rats in the control group. The lavage fluid of lungs from rats fed a high vitamin E diet (500 mg/kg diet) increased phagocytic activity of AM from rats fed a basal diet; it also induced a 72% increase in activity compared to that in control rats. The phagocytic activity of AM was not enhanced when the large molecules (MW greater than 10,000) were removed by ultrafiltration from the lavage fluid of lungs of rats fed the high vitamin E diet (500 mg/kg diet). These data suggest that there is macrophage-activating factor-like material in the lavage fluid of lungs of rats fed high vitamin E diets and that high vitamin E diets may activate not only splenic lymphocytes but also AM.

Immunosuppressive effects of dietary wortmannin on rats and mice.

In order to assess the effects of the fungal toxin wortmannin on the immune system, rats and mice were fed wortmannin-containing cultures of Fusarium oxysporum for 1 or 2 weeks. Wortmannin caused significant decreases in thymic weight, thymic lymphocyte numbers, serum IgG and IgM levels, the primary humoral response to T-dependent and T-independent antigens and the proliferative response of spleen cells to pokeweed mitogen. In vitro administration of wortmannin did not produce evidence of cytotoxicity to spleen or thymus cells. The data indicate that wortmannin inhibits immune function in rats and mice and suggest that metabolic modification of the toxin is necessary for toxicity.

Pavlovian conditioning of shock-induced supression of lymphocyte reactivity: Acquisition, extinction, and preexposure effects

Recent research has indicated that physical stressors, such as electric shock, can suppress immune function in rats. The present study investigated whether a nonaversive stimulus that had been associated with electric shock would also impair immune function. Presentation of that conditioned stimulus (CS) by itself produced a pronounced suppression of lymphocyte proliferation in response to the nonspecific mitogens, Concanavalin-A (ConA) and Phytohemagglutinin (PHA). In further evidence of a conditioning effect, the suppression was attenuated by extinction and preexposure manipulations that degraded the associative value of the CS. These results indicate that a psychological or learned stressor can suppress immune reactivity independently of the direct effect of physically aversive stimulation or of ancillary changes in dietary and health-related habits.

Immunological abnormalities in rats with adjuvant-induced arthritis — II. Effect of antiarthritic therapy on immune function in relation to disease development

The effects of the experimental immunomodulatory agent tilomisole (Wy-18,251; (3-(p-chlorophenyl) thiazolo [3,2-a]benzimidazole-2-acetic acid) on disease development and immune function in rats with adjuvant-induced arthritis was assessed in comparison with indomethacin and levamisole. Daily p.o. administration of tilomisole (100–200 mg/kg/day) to M. butyricum-injected rats significantly reduced both edema and bone erosion in the uninjected paw. Moreover, tilomisole treatment restored to normal the diminished Con A-induced proliferative response and IL 2 synthesis observed in spleen cells from arthritic rats, but had no effect on macrophage IL 1 production. In contrast, levamisole treatment (25 mg/kg/day) of arthritic rats improved splenic immune function but did not influence paw edema or bone erosion. Conversely, indomethacin (1 mg/kg/day) significantly reduced paw edema and bone erosion but did not improve the deficient proliferative response or IL 2 synthesis by “arthritic” spleen cells. These results indicate that tilomisole possesses combined antiinflammatory and immunomodulatory activity in adjuvant-arthritic rats which is distinctly different from the effects of either indomethacin or levamisole. Moreover, these data suggest that tilomisole has potential disease-modifying activity in arthritis, which is currently being more closely examined in clinical trials.

Stress, opioid peptides, the immune system, and cancer

Our results indicate that a particular form of footshock stress can suppress immune function in rats and decrease their resistance to tumor challenge. These effects appear to be mediated by opioid peptides released by stress, and they can be mimicked by high doses of morphine given systemically or by a vastly smaller dose delivered intracerebroventricularly. Such findings fit well into the emerging field of behavioral neuroimmunology and reinforce continuing efforts to elucidate the neural and neurohumoral mechanisms by which the environment can affect the organism's immune system.

Alterations in Immune Function in Rats Caused by Dietary Lipotrope Deficiency: Effect of Age

Weanling male Sprague-Dawley rats were maintained on a control (C), folacin-deficient (F) or marginal methionine-choline diet (M/C) for 3 weeks, 3 months or 12 months. The immunocompetence of the animals was determined by in vivo (response to infection with Salmonella typhimurium) and in vitro (lymphocyte transformation assay) methods. It was found that young animals were most sensitive to dietary lipotrope deficiency, and the in vivo response to bacterial infection did not always correlate with in vitro assessment of immune function. Histopathologic examination of spleens from S. typhimurium-infected rats maintained for 3 weeks on the experimental diets showed an overall decreased cellularity especially in the follicular area, compared to controls. No differences were seen in the spleens of infected animals at later time points. A short-term (3-week) lipotrope deficiency resulted in a depressed lymphocyte transformation response to concanavalin A (Con A) in the spleen, thymus and lymph nodes; to phytohemagglutinin A (PHA) in the spleen and lymph nodes only. After 3 months on the F or M/C diets, a depressed Con A-induced transformation response was still seen in the spleen, but the normal aging-induced immunosuppression resulted in a low response in all animals, with few significant differences existing among groups.immunocompetence lipotrope folacin methionine-choline

Alterations in Immune Function in Rats Caused by Dietary Lipotrope Deficiency: Effect of Culture Medium, 2-Mercaptoethanol and Mitogen Dose on the In Vitro Lymphocyte Transformation Response

The effect of variations in culture media, mitogen dose, harvest time, 2-mercaptoethanol (2-ME) addition and length of [3H]thymidine pulse on the concanavalin A (Con A)-stimulated splenic lymphocyte transformation response of male, weanling Sprague-Dawley rats maintained on a control (C), folacin-deficient (F) or marginal methionine-choline (M/C) diet was examined. Spenocytes cultured in minimal essential medium reached an optimal response on day 4. The response of F rats was significantly lower than C rats on day 3 and day 4. The response of M/C rats was lower on day 3. The addition of 2-ME to the culture medium shifted the cell cycle kinetics toward an earlier peak response time (day 2), and significant differences among groups were seen only under suboptimal conditions. Cells cultured in Medium 199 had a low transformation response, which reached peak stimulation on day 5. The response of F and M/C rats was significantly lower than C animals on days 3 and 4. In contrast, splenocytes cultured in medium 199 + 2-ME reached optimal stimulation on day 2, with no significant difference between groups. No effect on cell viability was seen from 2-ME, but it did accelerate cell cycle kinetics and reversed the normal age-induced immunosuppression seen in C animalsimmunocompetence lipotrope folacin methionine-choline 2-mercaptoethanol

Age-related changes in immune function of rats and the effect of long-term hypophysectomy

The effect of age on the ability of rats to raise antibodies to sheep erythrocytes and on the number of IgM plaque-forming cells in the spleen was investigated. An age-related decline in both parameters was observed. Additionally, the possibility that long-term hypophysectomy coupled with minimal hormone replacement therapy might result in a delay and/or reversal of the age-related decline in immune function was studied. It was observed that long-term hypophysectomized rats responded better to immunization with sheep erythrocytes than did their age-matched unoperated littermates. The possible relationship of this to aging is discussed.

I. Depressed immunological function in zinc-deprived rats as measured by mitogen response of spleen, thymus, and peripheral blood

The in vitro responses of splenic, thymic, and peripheral blood lymphocytes to two T-cell mitogens (phytohemagglutinin and concanavalin A) and one B-cell mitogen (pokeweed mitogen) were investigated in zinc-deprived and pair-fed control rats. The responses to phytohemagglutinin of splenic, thymic, and peripheral blood lymphocytes from zinc-deprived animals were depressed by at least 50% in comparison with those of controls, and the difference between the two groups was significant for each tissue (P = 0.05). The responses to concanavalin A of splenic and peripheral blood lymphocytes were suppressed in zinc-deprived animals, and splenic and thymic responses to pokeweed mitogen were depressed by about 50% in comparison with those of controls; these results were significant at the P = 0.05 level. This study is the first to evaluate the effects of diet-induced zinc deprivation on lymphocyte transformation and immune function in rats.