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R R Watson

Publications and source records attributed to R R Watson.

At least 91 records · Page 5Linked to original sources
PubMed1993

Cocaine modulation in vitro of tumor necrosis factor production by macrophages from retrovirally infected mice.

The effect of cocaine and LP-BM5 murine leukemia retrovirus infection on tumor necrosis factor (TNF) production were investigated. Three types of macrophages were used 1) peritoneal macrophage (PM), 2) thioglycollate induced peritoneal macrophage (TPM), and 3) alveolar macrophage (AM). Cells were cultured with and without cocaine during in vitro stimulation by lipopolysaccharide (LPS) and gamma-interferon (IFN). Retroviral infection enhanced the TNF production by PM and AM, but not by TPM. Intraperitoneal cocaine injection reduced TNF production by PM, but increased TNF production by AM and TPM. TNF production by AM from cocaine injected mice was stimulated by cocaine applied in vitro. In contrast, 100 micrograms/ml of cocaine in vitro significantly inhibited the TNF production by TPM from uninfected and retrovirally infected mice. Thus, TNF production by macrophages is modulated by murine retroviral infection and cocaine treatment. This could play an important role in host defense.

Animals↗
PubMed1993

Spleen and thymus cell subsets modified by long-term morphine administration in protein-undernourished mice--I.

Severe infections in intravenous drug abusers could be the consequence of morphine-induced damage on the immune system. To evaluate the long-term effect of in vivo morphine administration on the immune system we developed an experimental model where we studied the combined effects of morphine treatment and protein malnutrition. We treated protein-undernourished mice daily for 11 weeks with increasing doses of morphine. Morphine treatment produced a decrease in body weight and spleen cell number. The changes observed were partially independent of the nutritional status of the host. Saline-injected mice showed a decrease in the percentage of Thy 1+ cells in the spleen. Morphine treatment induced a decrease in the total number of cells and therefore in the absolute number of T-(Thy 1, CD4, CD8), B- and Mac 1+ (macrophages) cells in protein-undernourished mice. Saline-injected mice showed a decrease in the percentage of Thy 1+ cells and an increase in the percentage of B- and Ia(+)-cells in the spleen. We conclude that morphine altered the immune system by down-regulating splenocyte proliferation. We also studied the effects of i.p. administered morphine on expression of thymocyte phenotype in well-nourished and protein-undernourished mice. In well-nourished mice, morphine treatment reduced the number of Thy 1+, CD4+ and CD8+ cells per thymus to 30% of that found in untreated mice and to 40% of the cells in those saline-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Spleen and thymus cell subsets modified by long-term morphine administration and murine AIDS--II.

Intravenous heroin abusers suffer a great variety of infections, including AIDS (acquired immune deficiency syndrome). We developed an experimental mouse model to evaluate the long-term effect of in vivo morphine administration during retrovirus-induced immune dysfunction. Mice were treated daily for 11 weeks with increasing doses of morphine. Morphine treatment produced a decrease in body weight and spleen cell number. Murine retrovirus infection provoked an increase in body weight due to enlargement of lymphoid organs, and an increase in the percentage and absolute number of CD4+ and Mac 1+ cells. Interestingly, retrovirus-infected mice that were also morphine-treated did not show the increase in the relative proportion of Mac 1+ cells. Moreover, under the experimental conditions of protein-malnutrition and morphine treatment potentiation of immune dysfunction by murine retrovirus infection was investigated. Retrovirus infection-induced splenocyte proliferation was partially regulated by morphine treatment. Splenocytes from retrovirus-infected mice presented a higher percentage of IL-2R+ cells and, lower levels of sIL-2R in splenocyte supernatants. Mitogen-stimulated splenocytes had a lower production of interferon-gamma as well as an increase in the secretion of tumor necrosis factor-alpha. Thus morphine altered the immune system by down-regulating splenocyte proliferation, because retrovirus infection-induced splenocyte proliferation was partially regulated by morphine treatment. We also evaluated the effects of joint murine retrovirus infection and protein undernutrition on the thymus cell subsets. Retrovirus infection was associated with a decrease in the absolute number of Thy 1+, CD4+ and CD8+ cells per thymus with the CD8+ cell subset being the most affected. Moreover, retrovirus-infected mice presented a dramatic decrease in the percentage of double-positive (CD4+ CD8+) cells in the thymus as well as changes in its immunoarchitecture. While protein undernutrition alone did not produce further differences between infected versus non-infected, protein-undernourished, morphine treatment induced a greater decrease in thymocyte number than that seen in retrovirus- or morphine-treated animals alone.

Animals↗
PubMed1993

Enhancement of cocaine-induced hepatotoxicity by ethanol.

The contribution of moderate ethanol consumption on cocaine induced hepatotoxicity and the role lipid peroxidation plays as a possible mechanism of such increased hepatotoxicity were evaluated. Male C57BL/6 mice were injected interperitoneally (i.p.) with increasing doses of cocaine, from 10 to 50 mg/kg body weight daily and simultaneously fed a liquid diet containing 28% of the calories as ethanol for 5 or 9 weeks. Control mice received saline (i.p.) and an isocaloric carbohydrate diet. Lipid fluorescence and conjugated dienes of extracted lipids and amounts of malondialdehyde (MDA) were evaluated as indices of lipoperoxidation. In addition, serum alanine aminotransferase and aspartate transaminase were measured as indicators of liver injury and cellular death. After 9 weeks, ethanol consumption during cocaine treatment increased hepatic lipid fluorescence, conjugated dienes and MDA about twofold over mice-treated with cocaine alone. Similarly, serum transaminases were 2.8-6-fold greater in mice consuming alcohol and treated with cocaine than in mice treated with cocaine only. Histological examination of livers from mice fed ethanol during treatment with cocaine exhibited increased hepatic injuries and necrosis. The data suggest that ethanol exacerbates cocaine-induced hepatotoxicity via increases in free radical activity and hepatic lipid peroxidation.

Animals↗
PubMed1993

Resistance to intestinal parasites during murine AIDS: role of alcohol and nutrition in immune dysfunction.

A murine AIDS model with many similarities to human AIDS, LP-BM5 Murine Leukaemia, suppresses T and B cell numbers and functions in the intestine. This permits chronic colonization by Giardia and Cryptosporidium. Cocaine and the nutrient alcohol, which are immunosuppressive, further reduce resistance to intestinal parasites and intestinal lymphocyte numbers. Protein undernutrition, vitamin E supplementation, and alcohol use further modify immune dysfunction induced by the murine retrovirus infection. This suggests that both undernutrition and nutrient supplementation could affect parasite resistance during AIDS. Thus this murine model of human AIDS has great potential to accelerate studies of the role of nutrients in immune dysfunction and resistance to intestinal parasites.

AIDS-Related Opportunistic Infections↗
PubMed1993

Alcohol and murine acquired immunodeficiency syndrome suppression of resistance to Cryptosporidium parvum infection during modulation of cytokine production.

The effects of inoculation of LP-BM5 murine leukemia retrovirus and chronic ethanol (5% v/v) ingestion on immunomodulation and Cryptosporidium parvum infection in C57BL/6 female mice were evaluated. The intestinal mucosae of retrovirally immunosuppressed animals were heavily colonized by Cryptosporidium parasites, and oocysts shedding in the feces persisted throughout the duration of the study. Mortality was exacerbated by murine retrovirus infection alone and exacerbated with concomitant chronic alcohol feeding (42.8 and 69.4%). Chronic ethanol ingestion decreased production of interferon-gamma and soluble interleukin-2 receptor released in supernatants of splenocytes when stimulated with concanavalin A, compared with the control group. Decreased production of interferon-gamma and interleukin-2 receptor was further exacerbated due to retrovirus infection. Tumor necrosis factor production by splenocytes stimulated with lipopolysaccharide, however, was significantly increased because of retrovirus infection. LP-BM5 retrovirus infection alone as well as with concomitant ethanol feeding altered cytokine production, which might have led to immunodeficiency. These changes may help explain the enhanced persistence of Cryptosporidiosis.

Alcoholism↗
PubMed1993

Diet and ethanol modulate immune responses in young C57BL/6 mice.

Chronic ethanol (ETOH) ingestion adversely affects the immunocompetence of alcohol abusers. ETOH directly impairs host defense mechanisms and indirectly modulates immunocompetence by interfering with the nutritional status of the alcoholic. It is not clear from the current literature, however, to what extent ETOH, nutritional status, or the combination of the two factors modulates immune mechanisms in chronic alcoholics. To date, most animal studies investigating the immunotoxicity of ETOH have neglected the dietary factors, which may have masked additional immunotoxic effects of ETOH. To examine these dietary factors, we fed mice three liquid ETOH diets with different dietary sufficiencies for 7 weeks and investigated various immune responses. Spleen cell number and secretions of immunoreactive interleukin-2 and tumor necrosis factor were totally independent of the diet, being affected only by ETOH. Body, spleen, and thymus weights, interferon-gamma secretion, and natural killer cell and phagocytic activities were modulated by ETOH as well as by diet. Natural killer cell and phagocytic activities were also directly affected by the nutritional quality of the diet. These results suggest that animal diets used in experimental studies of ETOH-induced immunomodulation must be planned and controlled carefully in order to single out the direct effects that ETOH has on the host defense system.

Alcoholism↗
PubMed1993

Interleukin-6 and interleukin-8 production by mononuclear cells of chronic alcoholics during treatment.

Chronic alcohol consumption has been associated with suppression of a number of immune parameters. This study was designed to investigate the relationship between chronic alcohol ingestion and cessation with respect to release of interleukin-6 (IL-6) and interleukin-8 (IL-8) using highly specific and sensitive ELISA assays, as well as a functional assay, natural killer cell cytotoxic activity. ELISAs were developed to determine the amount of IL-6 and IL-8 release by peripheral blood mononuclear cells (PBMCs). Two groups of subjects were recruited: young (18-22 years old), nonalcoholic users (controls) and long-term alcoholics (35-55 years old). Blood samples were collected at time 0 from all subjects and from alcoholics 28 days after treatment had begun and alcohol use had ceased. Then mitogen-stimulated release of cytokines by peripheral blood cells was determined. The abstaining controls, and the alcoholics, after 30 days of abstinence, tended to produce lower amounts of IL-6 and IL-8, although these differences were not statistically significant. Natural killer cell activity was not statistically different between the young groups, yet appeared to increase once alcohol use discontinued. Some of the cells from the controls (abstainers) were incubated with ethanol (EtOH). Its content in sealed wells was measured after the time of incubation of PBMCs. When EtOH was serially diluted in plates, some well-well diffusion was noted, but the maximum concentration of EtOH never fell below 0.3% from an initial concentration of 0.5%, and at no time was the EtOH concentration gradient completely lost, even after 66 hr of incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Ethanol-induced modulation of cytokine production by splenocytes during murine retrovirus infection causing murine AIDS.

Ethanol (ETOH) consumption has been associated with general suppression of the immune response, resulting in increased susceptibility to infection. Chronic dietary ETOH consumption may be one of the cofactors accelerating development of human acquired immune deficiency syndrome (AIDS) after retrovirus infection. Chronic dietary ETOH [5% (v/v)] in the Lieber-DeCarli liquid diet was fed female C57BL/6 mice inoculated with LP-BM5 retrovirus causing murine AIDS for 11 weeks. Because cytokines are key regulators of humoral and cellular immunity, their production by concanavalin A (ConA) and lipopolysaccharide (LPS)-induced splenocytes was measured by ELISA methods. Decreased levels of interleukin (IL)-2 caused by retrovirus infection remained unchanged. Elevated levels of IL-5 and IL-6 produced in vitro by ConA-stimulated spleen cells during retrovirus infection were significantly further increased by dietary ETOH. Elevated IL-4 due to retroviral infection were not affected by dietary ETOH. Increased production of IL-10 induced by retrovirus infection, however, was significantly reduced by dietary ETOH, whereas decreased release of interferon-tau induced by retrovirus infection was significantly enhanced. Elevated levels of tumor necrosis factor-alpha produced by LPS-stimulated splenocytes from retrovirus infected mice were significantly further increased by dietary ETOH, whereas levels of IL-6 by LPS-stimulated splenocytes were not affected. Suppressed T-cell proliferation caused by retrovirus infection was significantly reduced further by dietary ETOH. However, no effect of dietary ETOH was observed on decreased B-cell proliferation by retrovirus infection. These results suggest that dietary ETOH aggravates progression of immune dysfunction leading to AIDS, because dietary ETOH modifies production of immunological regulatory cytokines.

Alcohol Drinking↗
PubMed1993

Enhancement of resistance to Cryptosporidium parvum by pooled bovine colostrum during murine retroviral infection.

The therapeutic efficacy of pooled bovine colostrum for the control of cryptosporidiosis was investigated during murine acquired immunodeficiency syndrome in female C57Bl/6 mice. Mice were infected with LP-BM5 murine leukemia retrovirus for four months and then inoculated with Cryptosporidium parvum oocysts. Persistent cryptosporidiosis was established in all retrovirus immunosuppressed mice, while control mice were refractory to infection. Parasite colonization of intestinal villi was significantly (P < 0.05) reduced in immunosuppressed animals that received dietary supplemental pooled bovine colostrum compared with to those that did not receive colostrum treatment. Similarly, shedding of oocysts in the feces of immunosuppressed animals that received dietary pooled bovine colostrum was significantly (P < 0.05) reduced compared with those that did not at 26 days post-parasite challenge. Since the nonimmune bovine colostrum contained no anti-Cryptosporidium antibodies, this suggests that passively transferred antibodies alone are unlikely to have provided the improved resistance shown in this study.

Animals↗
PubMed1993

Ethanol enhances immunosuppression induced by cocaine.

Use of cocaine concurrently with alcohol is prevalent among cocaine addicts. Cocaine has been shown previously to inhibit phytohemagglutinin- and ConA-induced proliferation of T-lymphocytes, NK cell cytotoxicity and phagocytic activity of peritoneal macrophages. We compared the immunotoxic effect of cocaine, combination of cocaine with ethanol, or cocaethylene, a derivative formed from cocaine and ethanol in the body, on the mitogen-stimulated production of cytokines by splenocytes. C57B1 mice were injected twice daily with 20 mg/kg cocaine or equivalent dose of cocaethylene and received a liquid Lieber-DeCarli diet containing ethanol (26% of total calories) or isocaloric amount of maltose-dextrin. After 4 weeks of treatment cocaine and cocaethylene caused a significant decrease of the spleen weight and total number of splenocytes. In splenocytes isolated from the cocaine- or cocaethylene-treated mice mitogen-stimulated production of gamma-interferon, tumor necrosis factor, and interleukin-2 was suppressed, in all cases more severely when cocaethylene was used. Thus formation of cocaethylene during simultaneous consumption of cocaine and ethanol may enhance the immunotoxicity of cocaine.

Alcoholism↗
PubMed1993

Ethanol modulation of tumor necrosis factor and gamma interferon production by murine splenocytes and macrophages.

C57BL/6 female mice were fed a liquid ethanol (ETOH) diet (27% of calories derived from ETOH) for 5 months as an animal model of chronic alcohol use. A isocaloric liquid diet supplemented with maltose dextran was fed to controls. Splenocytes from ETOH-treated and control mice, and purified macrophages from normal mice and retrovirus infected mice were exposed in vitro to various concentrations of ETOH (0.1-1.0% v/v). The effect of chronic ETOH exposure in vivo, and of in vitro treatment with ETOH on tumor necrosis factor (TNF) and gamma-interferon (IFN) production by cultured murine splenocytes and purified macrophages was investigated. Dietary ethanol did not significantly affect in vitro TNF or IFN production. However, TNF and IFN production by splenocytes from mice fed either the ETOH or control diet decreased significantly when the cells were cultured with ETOH and stimulated with LPS or Con A in vitro. Thus ETOH in vitro directly down regulates TNF and IFN secretion by LPS- or Con A-stimulated spleen cells. ETOH treatment in vitro did not significantly change TNF production by purified peritoneal macrophage (PM) and thioglycollate-induced peritoneal macrophage (TPM) from normal mice, but increased TNF production by alveolar macrophage (AM). Although murine retrovirus infection per se increased TNF production it did not change the responsive pattern in TNF production of PM and TPM to ETOH in vitro and reduced the TNF production of AM.

Animals↗
PubMed1993

Modulation of cancer growth by vitamin E and alcohol.

Seventy-five percent of esophageal cancers are alcohol related, yet alcohol is not a carcinogen. Ethanol may promote carcinogenesis via increased free radical products during its metabolism, as indicated by data from this and other studies. Ethanol is oxidized to acetaldehyde by alcohol dehydrogenase, catalase and the microsomal ethanol oxidizing system (MEOS). Free radicals (FR) are released during the oxidation of ethanol by the MEOS. An increased formation of FR in tissues would increase their oxidative stress and may increase their susceptibility for developing chemically induced cancers. FR and some FR products can rapidly react with biological materials, i.e. lipids, proteins and nucleic acids, forming toxic products. This study focuses on the effects of FR and/or FR products on cancer promotion during alcohol metabolism. Eight groups of mice were fed nutritionally adequate diets supplemented with vitamin E and/or ethanol. Some groups of mice were also orally gavaged with N-nitrosomethylbenzylamine (NMBzA), an esophageal carcinogen. Following the feeding of the various diets for 22 weeks, livers and esophagi were removed and the FR burden in the liver measured by the presence of lipid peroxide products and the number of tumors in each esophagus determined. These studies indicate that a linear relationship exists between the increasing number of esophageal tumors and increasing levels of lipid peroxide products that are formed during FR activity. These results show that FR and/or FR products are the cancer promoters during ethanol metabolism, since diets supplemented with high levels of vitamin E, which inhibits ethanol-induced FR activity and the formation of FR products, suppress the promotion of cancer by ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMed1993

Role of nutrients in alcohol-induced immunomodulation.

Immunosuppression observed in chronic alcohol users is caused by multiple factors including the amount of alcohol consumed and alcohol-induced nutritional deficiencies. Investigators of the immunotoxic effects of ethanol (ETOH) frequently concentrate on the effects of ETOH and neglect nutrition as a confounding variable. This study investigated the immunotoxic effects of ETOH under variable dietary nutritional conditions. Mice were fed diets containing various levels of nutrients and ethanol for 7 weeks. Spleen cell number, and interleukin-2 and tumor necrosis factor (TNF) secretion were independent of the diet consumed, but were affected by consumption of ETOH. Body and spleen weights, and interferon-gamma secretion were modulated by ETOH as well as by diet. The results indicate that the nutritional composition of the diet consumed during concurrent administration of ETOH modulates the immunotoxic effects of chronic ETOH ingestion. We conclude that the levels of various nutrients in animal diets have to be planned and controlled carefully in order to identify directly the immunotoxic effects of ETOH.

Alcohol Drinking↗
PubMed1992

Inhibitory effects of canthaxanthin on in vitro growth of murine tumor cells.

The antitumorigenic effects of carotenoids, in addition to their immuno-enhancing effects, may occur by their direct action on growing tumor cells. To test this hypothesis the direct inhibitory effect of various concentrations of canthaxanthin (CX; 4,4'-diketo-beta-carotene), a non-provitamin A carotenoid, was tested on the in vitro growth of JB/MS, B16F10 melanomas and PYB6 fibrosarcoma and murine non-transformed NIH-3T3 (ATCC CRL 1658) cells. At concentrations of 1 x 10(-8) M up to 1 x 10(-4) M, CX significantly reduced the overall number of tumor cells. The greatest inhibition was observed at a CX concentration of 1 x 10(-4) M after 72 h and 96 h of incubation. However, CX had no inhibitory effect on the growth of the non-transformed NIH-3T3 cell line; rather it significantly enhanced growth of this cell line (P less than 0.05) after 96 h of incubation. Thus, the inhibitory action of CX on growing tumor cells appears to be due to its direct actions on tumor cells and not via its conversion to vitamin A or its immuno-enhancing effects.

9,10-Dimethyl-1,2-benzanthracene↗