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Biomedical subjects

R R Watson

Publications and source records attributed to R R Watson.

At least 73 records · Page 4Linked to original sources
PubMed1994

In vivo and in vitro cocaine modulation on production of cytokines in C57BL/6 mice.

In the present study we used both in vivo and in vitro murine models to investigate the effects of cocaine on the release of cytokines (IL-1 alpha, IL-6, and TNF-alpha by peritoneal macrophages and splenocytes, IL-2, IL-4, IL-5, IL-10, and IFN-gamma produced by splenocytes. In vitro cocaine (0.1, 1, 10, 100 micrograms/ml) exposure inhibited all cytokines produced by ConA-stimulated spleen cells and LPS-stimulated macrophages in a concentration dependent manner. Different effects of cocaine administration on cytokine production were observed when female C57BL/6 mice were injected intraperitoneally with cocaine (40 mg/kg body weight for six weeks). Secretion of IL-2 by splenocytes was significantly enhanced by cocaine administration, whereas IFN-gamma was not affected. Secretion of IL-4 and IL-10 by splenocytes was significantly inhibited by cocaine administration, while secretion of IL-5 by splenocytes was significantly enhanced. Secretion of IL-6 and TNF-alpha by splenocytes was significantly enhanced by cocaine administration. Secretion of IL-6 by peritoneal macrophages was also significantly enhanced by the cocaine, while production of IL-1 alpha was not affected. However, release of TNF-alpha by peritoneal macrophages was significantly reduced by the cocaine administration. Therefore use of cocaine may alter the balance of cytokine production, and thereby adversely affects immune response and host defense.

Animals↗
PubMed1994

Effect of cocaine and murine AIDS on lamina propria T and B cells in normal mice.

We developed an experimental model to study the effect of daily cocaine administration on the mucosal immune system during murine acquired immune deficiency syndrome (MAIDS). Mice were infected with LP-BM5 murine leukemia virus, a retrovirus which causes immunosuppression with development of functional murine AIDS. Mice were given cocaine by daily intraperitoneal injection for 11 weeks. Our objective was to investigate if cocaine treatment could alter the mucosal immune system at the level of the intestinal lamina propria (ILP) and if it could further modify the already altered mucosal immunity when it was administered to MAIDS-mice. Daily cocaine administration induced a significant decrease in the number of IgA+ cells with a concomitant increase in the number of CD8+ cells per villi in the ILP. Murine retrovirus infection alone decreased the number of IgA+ and CD4+ cells in the ILP, and this decreased was even more marked when MAIDS mice also received cocaine. These data indicate that cocaine administration could potentiate the dramatic effect that MAIDS infection has in the mucosal-associated lymphoid tissues.

Animals↗
PubMed1994

Nutritional status and immune responses in mice with murine AIDS are normalized by vitamin E supplementation.

Female C57BL/6 mice were infected with LP-BM5 retrovirus, causing murine AIDS, which is functionally similar to human AIDS. Vitamin E effects on immune functions, cytokine production and nutritional concentrations in retrovirus-infected mice were determined. Retrovirus infection inhibited release of interleukin-2 (IL) and interferon-gamma (IFN) and some immune functions, whereas it stimulated secretion of IL-4, IL-5, IL-6 and tumor necrosis factor-alpha (TNF) and immunoglobulin (Ig) production. Furthermore, retrovirus infection induced some nutritional deficiencies in the tissues. A 15-fold increase in dietary vitamin E largely restored concentrations of some micronutrients (vitamins A and E, zinc and copper) in the liver, intestine, serum and thymus. It also partially restored production of IL-2 and IFN-gamma by splenocytes. Retrovirus-induced elevated production of IL-4, IL-5 and IL-6 by splenocytes in vitro was normalized by vitamin E. Elevated release of IL-6, TNF-alpha, IgA and IgG produced by splenocytes in vitro during murine AIDS were also completely or partially normalized by vitamin E. Vitamin E also prevented retrovirus-induced suppression of splenocyte proliferation and natural killer cell activity. These data indicate that vitamin E supplementation during murine AIDS can help to ameliorate the disorders during murine AIDS, suggesting vitamin E usefulness in treatment of AIDS in humans.

Animals↗
PubMed1994

Dietary vitamin E modulation of cytokine production by splenocytes and thymocytes from alcohol-fed mice.

As vitamin E enhances immune responses, it may reduce dietary ethanol (EtOH)-induced immune suppression, thereby favorably affecting host disease resistance. The effects of dietary vitamin E at higher level in alcohol-fed female C57BL/6 mice was determined via in vitro cytokine production by splenocytes and thymocytes, and some other immune functions. A 15-fold increase of vitamin E (160 IU/liter) in a liquid diet (National Council Research), with or without EtOH (4.5%, v/v), was fed to mice for 10 weeks. Vitamin E supplementation restored production of interleukin-2, -5, -6, -10, and interferon-gamma by concanavalin A (Con A)-stimulated splenocytes and interleukin-6 and tumor necrosis factor-alpha by lipopolysaccharide-stimulated splenocytes, which were suppressed by dietary EtOH. However, it had no effect on interleukin-4 secretion, which was also reduced by splenocytes from EtOH-fed mice. Vitamin E supplementation also restored EtOH-suppressed, mitogen-induced splenocyte proliferation, but not thymocyte proliferation, although it slightly increased production of immunoglobulin A and G by lipopolysaccharide-stimulated splenocytes, which were suppressed by dietary EtOH. Dietary vitamin E, furthermore, significantly increased interleukin-2 and -6 secretion by Con A-stimulated thymocytes, which were suppressed by dietary EtOH, although it had no effect on interleukin-4 and interferon-gamma production by Con A-stimulated thymocytes from EtOH-fed mice. These data suggest that dietary vitamin E supplementation can modulate dysregulation of cytokines initiated by dietary EtOH and restore immune dysfunctions induced by EtOH ingestion.

Alcoholism↗
PubMed1994

Ethanol consumption and early murine retrovirus infection influence liver, heart, and muscle levels of iron, zinc, and copper in C57BL/6 mice.

The relative and combined roles of ethanol and murine acquired immunodeficiency syndrome (MAIDS) on the mineral status (Fe, Zn, and Cu) of liver (storage site), heart, muscle (nutrient mobile sites) were investigated. C57BL/6 mice were randomly assigned to four groups: (a) uninfected mice fed isocaloric, adequate nutrient diet (NRC), (b) uninfected mice fed the NRC diet with 25% of energy derived from ethanol, (c) LP-BM5 retrovirus-infected mice fed the isocaloric NRC diet, and (d) retrovirus-infected mice fed the NRC diet with 25% of its energy derived from ethanol. The levels of Cu and Zn levels in the liver did not significantly change as a result of ethanol consumption. However hepatic Zn concentration was increased significantly in retrovirus-infected mice. This may be correlated to the increase in their liver weight. Ethanol administration significantly increased Fe concentration in the liver, yet significantly decreased concentration of Cu in the heart. Retrovirus infection alone, which had not proceeded to murine AIDS, resulted in a significant increase in heart Cu and Zn concentration as compared with uninfected mice. Retrovirus infection in C57BL/6 mice significantly increased Fe and Zn level/g of muscle. Early retrovirus infection alters tissue micronutrient levels, and may thus contribute to immunological changes.

Alcoholism↗
PubMed1994

Chronic ethanol consumption before retrovirus infection is a cofactor in the development of immune dysfunction during murine AIDS.

Chronic ethanol (EtOH) consumption has been presumed to be a cofactor in the development of acquired immune deficiency syndrome (AIDS). AIDS is identified as a major public health priority in the United States, with heavy economic and social impact. In the present study, we tested this hypothesis that EtOH users are more predisposed to immunosuppression because of retrovirus infection in murine AIDS. Adult female C57BL/6 mice were fed 4.5% (v/v) in liquid diet and control diets for 10 weeks. Then all mice were infected with LP-BM5 retrovirus, causing murine AIDS, and were fed control liquid diets without EtOH. Interleukin (IL)-2 production produced by concanavalin A (Con A)-stimulated splenocytes was suppressed during murine AIDS. It was further inhibited in EtOH-fed mice compared with controls at 6 weeks postinfection, whereas decreased level of interferon-gamma during murine AIDS was not further affected in EtOH-fed mice. The levels of IL-5, IL-6, and IL-10 secreted by Con A-induced splenocytes, elevated during murine AIDS, were significantly further enhanced in EtOH-fed mice compared with controls at 6 weeks postinfection, whereas retrovirus-induced elevated release of IL-6 and tumor necrosis factor-alpha, produced by lipopolysaccharide (LPS)-stimulated splenocytes, were further increased in EtOH-fed mice compared with controls at 6 and 9 weeks postinfection, respectively. Con A- and LPS-induced splenocyte proliferation, inhibited by retrovirus infection, was significantly further suppressed in EtOH-fed mice compared with controls. These results suggest that dietary EtOH consumption before retrovirus infection aggravated progression of immune dysfunction, because it modified production of immunological regulatory cytokines and immune functions.

Alcoholism↗
PubMed1994

Modification of lymphocyte subsets in the intestinal-associated immune system and thymus by chronic ethanol consumption.

Modification of the mucosa-associated intestinal immune system of female C57BL/6 mice was studied during consumption of the Lieber-DeCarli diet supplemented with 5% v/v ethanol or laboratory chow with ethanol (20% w/v) in the drinking water. All groups received ethanol for 11 weeks. Mice fed the Lieber-DeCarli diet had fewer CD8+ cells/villus than the chow-fed controls. Mice that received ethanol in the drinking water had fewer IgA-containing cells and CD8+ cells than controls. There were no differences in the number of cells in the mesenteric lymph nodes between ethanol-treated mice and their respective controls. Nevertheless, chow-fed control mice had more cells than those fed the Lieber-DeCarli control diet. Although no differences were detected in the percentages of CD4+, CD8+, LECAM-1+, and LECAM-1+ CD4+ cells, there was a decrease in the percentage of LECAM-1+ CD8+ cells in ethanol-fed mice when compared with their Lieber-DeCarli controls. Mice receiving ethanol in the drinking water showed alterations in the CD4 CD45RC subsets and in the CD8 CD45RC subsets. Similar results were observed in mice receiving Lieber-DeCarli diets alone or supplemented with ethanol. The low dose, chronic exposure of dietary ethanol in the Lieber-DeCarli-fed mice did not significantly affect the numbers of various thymocyte subsets. But, a decrease in the percentage of CD4- CD8+ cells was observed in the thymus of mice receiving ethanol in the drinking water. Chronic ethanol consumption caused significant decreases in the number of CD8+ and IgA+ cells in the intestinal lamina propria, important in mucosal immune defenses.

Alcoholism↗
PubMed1994

Influence of chronic dietary ethanol on cytokine production by murine splenocytes and thymocytes.

Prolonged consumption of ethanol (ETOH) results in alterations of host defense via immune modulation, increasing susceptibility to infection. In the present study, effects of chronic dietary ETOH on cytokine production by splenocytes and thymocytes, splenocyte and thymocyte proliferation induced by mitogens, splenic natural killer cell activity, and antibody production (IgA and IgG) were examined. C57BL/6 mice were fed 5% ETOH v/v in the Lieber-DeCarli liquid diet for 11 weeks. Release of interleukin (IL)-2, IL-5, IL-6, IL-10, and interferon (IFN)-gamma produced by concanavalin A (Con A) stimulated splenocytes was significantly decreased, whereas secretion of IL-4 was slightly decreased by chronic dietary ETOH compared with controls. Production of tumor necrosis factor-alpha and IL-6 by lipopolysaccharide-stimulated splenocytes was significantly and slightly decreased by ETOH compared with controls, respectively. Splenocyte and thymocyte proliferation induced by Con A was significantly inhibited by ETOH, whereas splenocyte proliferation induced by lipopolysaccharide was not affected. Natural killer cell activity was significantly inhibited by ETOH compared with controls. The production of IgA and IgG by splenocytes were also significantly decreased by ETOH compared with controls. The levels of IL-2, IL-4, and IL-6 produced by Con A-stimulated thymocytes were significantly reduced by dietary ETOH compared with control, whereas production of IFN-gamma by thymocytes was not affected. Our results suggest that chronic dietary ETOH alters the cytokine release, thereby impairing immune response and T-cell maturation, which increase host susceptibility to infection.

Alcoholism↗
PubMed1994

Anti-IL-4 monoclonal antibody and IFN-gamma administration retards development of immune dysfunction and cytokine dysregulation during murine AIDS.

This study was designed to determine if administration of anti-interleukin-4 (IL-4) monoclonal antibody (mAb), interferon-gamma (IFN-gamma) and their combination after LP-BM5 retrovirus infection of female C57BL/6 mice would prevent retrovirus-induction of immunosuppression and cytokine dysregulation. Splenic natural killer (NK) cell activity, T- and B-cell proliferation, and T-helper type 1 (Th1) and Th2 cytokine (IL-2, IFN-gamma, IL-5 and IL-10) and monokine [IL-6 and tumour necrosis factor-alpha (TNF-alpha)] secretions were monitored, as they are usually altered dramatically after murine retrovirus infection. Administration of IFN-gamma and anti-IL-4 significantly prevented retrovirus-induced suppression of splenic NK cell activity, and splenic T- and B-cell proliferation. They also significantly slowed retrovirus-induced elevation of Th2 cytokine (IL-5 and IL-10) release and monokine (IL-6 and TNF-alpha) secretion by splenocytes. They prevented the loss of Th1 cytokine (IL-2 and IFN-gamma) release by splenocytes, and alleviated splenomegaly and hypergammaglobulinemia, precursor signs of development of acquired immune deficiency syndrome (AIDS). These findings could provide insight into the roles of immunomodulator in AIDS treatment as well as the mechanisms by which retrovirus infection induces cytokine dysregulation, facilitating immunodeficiencies in AIDS.

Animals↗
PubMed1994

Vitamin E supplementation at various levels alters cytokine production by thymocytes during retrovirus infection causing murine AIDS.

Female C57BL/6 mice were infected with LP-BM5 retrovirus, causing murine AIDS which is functionally similar to human AIDS. Retrovirus infection targets the thymus producing altered T-cell differentiation via the dysregulation of thymocyte cytokine production. Therefore the effects of dietary vitamin E at various levels were determined on cytokine production by ConA-stimulated thymocytes from uninfected (normal) and retrovirus-infected mice. Dietary supplementation, with a 15-, 150- and 450-fold increase of vitamin E in the diet modulated interleukin-2 (IL) production in both uninfected mice and retrovirus-infected mice. The 150- and 450-fold vitamin E supplementation significantly reduced IL-4 secretion by thymocytes from the uninfected, normal mice. Supplementation at all levels also significantly reduced IL-4 production by thymocytes, which was elevated by the retrovirus infection. Vitamin E significantly reduced IL-6 and interferon-gamma production increased during the progression to murine AIDS. The effects of dietary vitamin E on conA-induced proliferation of thymocytes were consistent with the finding on changes of IL-2 secretion. No effect of dietary vitamin E on thymus weight was observed in both uninfected and retrovirus-infected mice. These data indicate that dietary vitamin E supplementation at extremely high levels can modulate cytokine production by thymocytes. This could affect T-cell differentiation, especially during murine AIDS when cytokine production was partially normalized by vitamin E supplementation.

Animals↗
PubMed1994

Alcohol, immunomodulation, and disease.

Recent research findings point to a spectrum of alcohol-induced immune dysfunctions in animal models and humans. Use of alcohol in vivo causes abnormalities in the function and/or structure of a broad array of cells involved in humoral and cellular immunity, including lymphocytes, Kupffer cells and other macrophages, as well as the endothelium of blood vessels and lymphatics. Regulatory cytokines and neuroendocrine factors can mediate some of these immunomodulatory effects which may be further re-phased, exaggerated or unbalanced by other drugs of misuse. A variety of animal models is available to study acute and chronic alcoholism, non-alcohol drug misuse, AIDS as well as other opportunistic infections, and neoplasias, which hold promise of clarifying the role of alcohol as an immunomodulator.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Influence of beta-carotene on immune functions.

Recent reports have demonstrated that beta-carotene, a nontoxic carotenoid, is able to stimulate immune functions in humans. The purpose of this study is to understand the mechanisms of immunoenhancement by carotenoids in order to explain their anticancer effects. We have evaluated the clinical efficacy of beta-carotene, given 30 mg/day orally, for treatment of oral leukoplakia patients. Patients who responded to beta-carotene treatment showed increased plasma levels of TNF-alpha. Epithelial cells from these patients were characterized in vitro. These results may lead to a better understanding of the therapeutic use of beta-carotene in humans.

Adjuvants, Immunologic↗
PubMed1993

Reduction of tumor necrosis factor production by splenocytes from v-Ha-ras oncogene-bearing mice.

Mice containing the activated v-Ha-ras oncogene driven by the mouse mammary tumor virus promoter/enhancer produced less tumor necrosis factor (TNF) than genetically identical animals without it. Inbred Oncomice containing the v-Ha-ras oncogene and inbred FVB mice without it were grown for 6 months. Splenocytes were isolated and stimulated in vitro to produce tumor necrosis factor (TNF) and gamma-interferon (IFN). TNF production by cells from Oncomice was significantly decreased compared to cells from FBV mice. There was a tendency for decrease, but no significant difference was seen on IFN release. These observations suggest that the oncogene may play a role in the immune system.

Animals↗
PubMed1993

Cocaine facilitation of cryptosporidiosis by murine AIDS in male and female C57/BL/6 mice.

As cocaine may affect progression of the Human Immunodeficiency Virus (HIV) infection to Acquired Immune Deficiency Syndrome (AIDS), we used a murine model of AIDS (MAIDS) induced by LP-BM5 murine leukemia virus to examine cocaine's possible role as a cofactor for secondary parasitic infections. Dissimilarities between the sexes were observed both in the absence and presence of the cocaine. The retrovirus-infected female mice had a much higher rate of Cryptosporidiosis than the retrovirus-infected male mice. Female, but not male, retrovirus-infected mice showed approximately 20-fold more Cryptosporidium per villus section than controls. Compared to respective gender controls, male and female animals infected with the retrovirus infection manifested a heightened Cryptosporidium oocysts count regardless of cocaine treatment. Overall, female groups incurred a higher incidence of infection compared to respective male groups. To determine the role of cocaine, groups of male and female C57BL-6 mice of similar age were treated with cocaine for 4 weeks followed by termination. Cocaine synergized with retrovirus infection in female mice to cause a 30-fold increase in the number of oocyst present. The spleen size and weight of female mice was significantly greater than uninfected controls or male mice. However, due to the very slow progression to murine AIDS in the males, parasite resistance was retained, including in cocaine treated C57BL-6 mice. Thymus cell number in the retrovirus-infected female mice decreased significantly in comparison to uninfected female controls. Continued resistance to the parasite in male mice and its loss in female mice was due to the rate of immunosuppression and thus development of retrovirus-induced murine AIDS.

Animals↗
PubMed1993

Suppression by dietary alcohol of resistance to Cryptosporidium during murine acquired immune deficiency syndrome.

Significant immunological changes occur following LP-BM5 murine leukemia retrovirus infection as well as chronic alcohol consumption. Retrovirus infection which has proceeded to murine AIDS permitted persistent Cryptosporidium infection, while non-retrovirus infected mice were resistant. Dietary alcohol provided until the day before parasite challenge did not affect resistance in controls, but increased the numbers of oocysts in the feces of retrovirus suppressed mice. Mortality was significant in retrovirus infected mice, and exacerbated slightly by dietary ethanol, while all controls survived parasite challenge. The retrovirus infected mice had greatly reduced numbers of intestinal CD4+ T helper cells and IgA+ B cells, which may explain their loss of intestinal resistance. Clearly, the severely immunosuppressed animals with murine AIDS were more sensitive to alcohol consumption than uninfected controls. This suggests that alcohol can synergize with murine retrovirus infection to exacerbate loss of resistance to an opportunistic pathogen common in human AIDS patients.

Animals↗
PubMed1993

Vitamin E supplementation modulates cytokine production by thymocytes during murine AIDS.

Female C57BL/6 mice were infected with LP-BM5 retrovirus, causing murine AIDS, which is functionally similar to human AIDS. Retrovirus infection targeted the thymus, producing altered T cell differentiation via the dysregulation of thymocyte cytokine production. Human AIDS causes vitamin deficiencies, therefore the effects of dietary vitamin E supplementation were determined on the kinetics of cytokine production by concanavalin A-stimulated thymocytes in uninfected normal mice and mice with murine AIDS. Dietary supplementation, with a 15-fold increase in vitamin E (160 IU/l) in the liquid diet (National Research Council), modulated interleukin-2 (IL) production in both uninfected mice and retrovirus-infected mice. Vitamin E significantly reduced the level of IL-4 secretion in the uninfected mice at 4 and 8 weeks, but not at 12 and 16 weeks. It also significantly reduced IL-4 production, elevated by retrovirus infection. Vitamin E significantly reduced IL-6, and interferon-gamma production increased in murine AIDS. The effects of dietary vitamin E on concanavalin A-induced proliferation of thymocytes were consistent with the finding of changes in IL-2 secretion. No effects of dietary vitamin E on thymus weight were observed in uninfected or retrovirus-infected mice, whereas vitamin E significantly increased serum and thymic vitamin E concentration, which had been reduced by retrovirus infection. These data indicate that dietary vitamin E supplementation can modulate cytokine production by thymocytes, affecting T cell differentiation, especially during retrovirus-induced immune dysfunction.

Animals↗