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PubMed2003

Ecotoxicological risks associated with land treatment of petrochemical wastes. III. Immune function and hematology of cotton rats.

Landfarming is a widely used method of treating petrochemical waste through microbial bio-degradation. The effects of residual petrochemical contamination on wildlife, especially terrestrial mammals, are poorly understood. The effects of contaminants on the immune system and hematology of cotton rats (Sigmodon hispidus) living on five abandoned petrochemical landfarms (units 1-5) in Oklahoma were studied. Cotton rats were sampled seasonally (summer and winter) from each landfarm and from five ecologically matched reference sites for 2 yr (1998-2000) and returned to the laboratory for immunological and hematological assays. Overall analysis indicated that rats inhabiting landfarms exhibited decreased relative spleen size compared to rats collected from reference sites, with the landfarm at unit 1 showing the greatest reduction. Cotton rats collected from landfarms also had increased hemoglobin, hematocrit, and platelet levels and decreased blood leukocytes during summer. During winter, an increase in the number of popliteal node white blood cells was observed from rats collected on landfarms. No marked difference was detected for lymphocyte proliferation in response to concanavalin A, pokeweed, or interleukin-2. Lymphokine-activated killer cell lytic ability showed a seasonal pattern, but no treatment differences. No differences between landfarm and reference sites were detected in the hypersensitivity reaction of rats given an intradermal injection of phytohemagluttinin (PHA-P). Comparisons within individual sites indicated that two sites (units 1 and 3) had the greatest effects on immune function and hematology of cotton rats. The results of this study suggest that residual petrochemical waste affects the immune system and hematology of cotton rats living on abandoned landfarms during summer and is complicated by variation in the contaminants found on individual petroleum sites.

Agriculture↗
PubMed2003

Skin cancer and non-Hodgkin's lymphoma as second malignancies. markers of impaired immune function?

Successes in cancer therapy have led to increasing numbers of cancer survivors, who are at risk of developing second primary cancers. Therapy- or disease-induced suppression of the immune function may predispose cancer patients to a second malignancy. An excess of squamous cell skin cancers (SCC) and non-Hodgkin's lymphomas has been found in immunosuppressed patients. We used the nationwide Swedish Family-Cancer Database on 10.2 million individuals to calculate the risk of second primary skin cancers and non-Hodgkin's lymphomas following a previous malignancy. A total of 4301 second skin cancers and 1672 non-Hodgkin's lymphomas were identified. Standardised incidence ratios (SIR)s and 95% Confidence Intervals (CIs) were calculated and compared. Among 14 different sites for male or female first primary malignancies, 11 of these sites were followed by an increased risk of skin cancer (SIRs for males for risk of skin cancer as a second primary cancer: 14.1 for SCC; 9.7 for melanoma; 6.1 for leukaemia as the first site; SIRs for females for risk of skin cancer: 14.6 for SCC; 6.8 for larynx; 6.2 for upper aerodigestive tract (UADT) as the first site). The risk of non-Hodgkin's lymphoma was increased after 10 of 14 different male neoplasms and 12 of 17 different female neoplasms. (SIRs for males for risk of non-Hodgkin's lymphoma as a second primary cancer: 6.4 for non-Hodgkin's lymphoma; 3.2 for leukaemias; 3.1 for multiple myeloma as the first site; SIRs for females for risk of non-Hodgkin's lymphoma as a second primary cancer: 12.5 for leukaemias; 7.0 for Hodgkin's disease; 3.6 for UADT as the first site). The high, and after certain sites, very high risks of second skin cancer and non-Hodgkin's lymphoma suggest that immune suppression may be a contributory mechanism.

Carcinoma, Squamous Cell↗
PubMed1990

Evaluation of human cellular immune function in echinococcosis.

Forty nine individuals (11 patients with surgically proved hydatid disease, 23 individuals with non hydatid disease and 15 normal healthy adults) were investigated for specific and nonspecific cellular immune status using in vitro blast transformation assay. Patients with hydatid disease had suppressed cellular immune function to a nonspecific T-cell mitogen (PHA) when compared to the relevant controls. Hydatid antigen directly inhibited in vitro blast transformation from a concentration of 0.1 microgram protein/ml onwards in all the three groups of subjects, irrespective of whether they had hydatidosis or not. However, hydatid antigen did not act as a T-cell mitogen in our study.

Animals↗
PubMed2005

Interferon alpha2b augments suppressed immune functions in tobacco-related head and neck squamous cell carcinoma patients by modulating cytokine signaling.

We have examined the role of interferon alpha2b (IFNalpha2b) in augmentation of the suppressed immune functions and cytotoxicity of tobacco-related head and neck squamous cell carcinoma (HNSCC) patients. The suppressed killing activity of PBMC of HNSCC patients towards KB, MCF7 and K562 cell lines could be restored by in vitro treatment of PBMC with IFNalpha2b, as detected by LDH release assay. HNSCC patients with cisplatin + 5FU + IFNalpha2b treatment showed greater cytotoxic efficacy than corresponding pretreatment values. Analysis of culture supernatant of HNSCC-PBMC by ELISA revealed the lower secretion of IL-12 and IFNgamma with increased level of IL-4 and IL-10. This altered Th1/Th2 status was rectified after in vitro and in vivo IFNalpha2b stimulation. Increased secretion of monocyte derived IL-12 was observed after IFNalpha2b treatment that can enhance the IFNgamma release, a key regulator for cytotoxicity. IFNalpha2b stimulated enhancement of NK cells may be the source of greater amount of IFNgamma. IFNalpha2b activated STAT1 and STAT4 signaling is observed to be involved in the regulation and maintenance of cytokine milieu. We conclude that IFNalpha2b may be effective as a tool for adjuvant therapy along with conventional therapies to overcome the immunosuppression in HNSCC patients.

Adult↗
PubMed1994

Mast cell-mediated colonic immune function and its inhibition by dietary aspirin in mice infected with Trichinella spiralis.

Because of the integrated nature of cellular elements in the gut wall, an understanding of the local mucosal immune system and its adaptive capacity should provide more insight into diseases of the colon, such as inflammatory bowel disease and colorectal cancer. To develop a method to quantify colonic mucosal immune function in situ, ion transport mediated by a type I hypersensitivity reaction was measured in the colon of mice infected with Trichinella spiralis. Segments of sensitized distal colon mounted in Ussing chambers and challenged with T. spiralis-derived antigen resulted in a rise in short-circuit current (delta Isc) that was antigen-specific and inhibited by furosemide. Colonic segments from infected, mast cell-deficient W/Wv mice were unresponsive to challenge with T. spiralis antigen. Inhibition of anaphylactic mediators with various pharmacological agents implicated prostaglandins and leukotrienes as the principal mediators of the antigen-induced delta Isc, with 5-HT also playing a role. Neural blockade with tetrodotoxin or blockade of histamine H1 receptors with diphenhydramine failed to inhibit the colonic immune response. Distal colon from immune mice fed an aspirin-containing diet (800 mg/kg powdered diet) ad libitum for 6 weeks had a decreased response to antigen. However, dietary aspirin had no effect on antigen-induced delta Isc in the jejunum or on Cl- secretagogue-stimulated delta Isc in the distal colon. These results suggest that products of arachidonic acid metabolism are important mediators of mast cell-dependent, antigen-stimulated Cl- secretion in the distal colon of mice immunized by infection with T. spiralis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Lithium and immune function.

Lithium has potent antiviral and immunostimulating properties which are probably consequences of its actions on prostaglandin synthesis. Although lithium has considerable potential in the prophylaxis of some viral illnesses and other manifestations of defective immune function, it is, paradoxically, capable of activating autoimmune mechanisms in predisposed patients.

Adjuvants, Immunologic↗
PubMed1997

[The characteristics of the development of the immune function in the transplanted spleen of newborn mouse pups in recipients of different ages. I. The effect of the cells in the stromal microenvironment of the transplant].

The age-related changes in the cell composition, immune response to SRBC and proliferative activity of T- and B-cells in vitro were determined in neonatal spleen grafted to CBA/Ca female mice of different ages. The dependence of the immune response upon the recipient's age was observed. This result indicate that "young" transplant stromal cells are incapable of immune response increase in the old recipients. Analysis of the T- and B-cells content in the spleen grafted to the recipients of different ages demonstrated no differences. The decrease of the T-cell proliferative activity and existence of the inverse correlative connection between content of the T-cells and PFCs in spleen grafted to the old recipients were demonstrated. Additional neonatal thymus transplantation is proposed as tools for correction of the age-related changes in the immune function.

Aging↗
PubMed1989

Glutamine-supplemented total parenteral nutrition improves gut immune function.

Glutamine has been demonstrated to be an important source of fuel for the gut. The purpose of this study was to evaluate the effect of glutamine-supplemented hyperalimentation on gut immune function. Thirty-six female Fischer rats were randomized into three groups: group 1 (chow) was fed rat chow and water ad libitum, group 2 (total parenteral nutrition) received a standard hyperalimentation formula, and group 3 (total parenteral nutrition-glutamine) received a hyperalimentation solution that contained 2% glutamine. Animals were maintained on their respective diets for 2 weeks and then killed. Mesenteric lymph nodes were harvested for culture, bile was assayed for secretory IgA, and bowel was excised to assay bacterial adherence. Results indicated that glutamine-supplemented total parenteral nutrition protects against bacterial translocation from the gut seen with standard formulas. This effect may be mediated by the secretory IgA immune system.

Animals↗
PubMed2000

[Effect of hyperthermia on the red-cell immune function of rats and its teratogenicity on developing embryos].

After rats on gestation day 10 exposed to hyperthermia(40 degrees C) for 0.5, 1.0, 2.5 and 5.0 h, red-cell C3b receptor activity(aggregate), red-cell immune complex, circulating immune complex, Nile blue sulfate (NBS) vital staining, electronic microscope and histochemical techniques were used in investigate whether the hyperthermia was disturb red-cell immune functions of pregnant rats and played some role in teratogenesis. The results showed that hyperthermia increased the level of red-cell C3b receptor activity, red-cell immune complex and circulating immune complex. On the other hand, many of them also decreased to normal level after rats were placed in room temperature for 20 h. Following the extension of hyperthermic exposure, the teratogenic incidence increased from 0.9%(1/117) to 18.3%(22/120), in apparent time-effect relationship, when pregnant rats of gestation day 11.5 were killed. It was found that hyperthermia induced.

Animals↗
PubMed2005

Dietary effect of pomegranate seed oil on immune function and lipid metabolism in mice.

OBJECTIVES: We evaluated the effects of dietary pomegranate seed oil (PSO), which contains high levels of punicic acid (9c, 11t, 13c-octadecatrienoic acid), on immune function and lipid metabolism in C57BL/6N mice. METHODS: Mice were fed experimental diets containing 0%, 0.12%, or 1.2% PSO for 3 wk. RESULTS: No significant differences were observed between growth patterns of the experimental groups. Splenocytes isolated from mice fed 0.12% or 1.2% PSO produced larger amounts of immunoglobulins G and M but not immunoglobulin A irrespective of stimulation with or without phorbol 12-myristate 13-acetate and the calcium ionophore A23187. Dietary PSO did not affect the percentages of B cells or CD4-positive or CD8-positive T cells in splenocytes. Levels of interleukin-4, interferon-gamma, and tumor necrosis factor-alpha production from splenocytes were comparable among all dietary groups. Analysis of serum lipid parameters showed significant increases in serum triacylglycerol and phospholipid levels but not in total cholesterol in the PSO groups. Serum, liver, epididymal, and perirenal adipose punicic acid levels were high with increases in dietary PSO level. However, punicic acid was not detected in splenocytes for any dietary group. Interestingly, 9c, 11t-conjugated linoleic acid level could be detected in serum, liver, and adipose tissues in mice fed the 0.12% or 1.2% PSO diet. CONCLUSIONS: These results suggest that PSO may enhance B-cell function in vivo.

Animals↗
PubMed2003

Effect of spleen on immune function of rats with liver cancer complicated by liver cirrhosis.

OBJECTIVE: To establish a rat model of liver cancer complicated by liver cirrhosis and explore the effects of the spleen on immune function in this model. METHODS: Liver cirrhosis was inflicted in rats by percutaneous injection of 40% CCl4 on the back. Walker-256 tumor cells were inoculated in the cirrhotic liver and splenectomy was performed. Two weeks later, the growth and metastasis of tumor were observed and the amount of ascites and the activity of NK cells and CD25 cells were investigated. RESULTS: The amount of ascites and tumor volume were significantly higher in splenectomy group than in controls (P<0.01). Two weeks after inoculation, the activity of NK cells in both groups was decreased as compared with that before the inoculation (P<0.01). There was no significant difference between the two groups before and after the inoculation (P>0.05). The number of CD25 in both groups was higher than that before the inoculation (P<0.01). However, there was no significant difference between the two groups before and after the inoculation (P>0.05). CONCLUSIONS: Splenectomy in early stage of tumor inoculation can stimulate the tumor growth and metastasis. The activity of NK cells and the number of CD25 are inhibited by tumor itself, not by splenectomy.

Animals↗
PubMed1995

Immune function in athletes versus nonathletes.

The purpose of this study was to compare natural killer cell cytotoxic activity (NKCA) and Con A-induced lymphocyte proliferation (T cell function) in athletes versus nonathletes, with measurement of natural killer (NK) and T cells to allow a comparison on a "per-cell" adjusted basis. Eighteen young male endurance athletes (10 runners and 8 cyclists) with a mean VO2max of 70.7 +/- 1.3 ml.kg-1.min-1 and 6.6 +/- 0.8 years of competitive experience were compared with 11 nonathletic male adults (47.6 +/- 3.1 ml.kg-1.min-1). Concentrations of circulating leukocyte and lymphocyte subsets, including NK and T cells, were not significantly different between groups. NKCA and T cell function also did not differ between groups, whether expressed unadjusted or adjusted on a per-cell basis. For all subjects combined, both NKCA and T cell function were unrelated to VO2max (r = 0.005, p = 0.98; r = 0.007, p = 0.97, respectively). These data do not support the contention that immune function, as measured in this study, is altered in endurance athletes.

Adult↗
PubMed1995

Fumonisin B1 alters sphingolipid metabolism and immune function in BALB/c mice: immunological responses to fumonisin B1.

Fumonisins have been reported to have diverse effects on animals, including immunosuppression in chickens and feeder calves; therefore, the effects of fumonisin B1 (FB1) on immune function in BALB/c mice was investigated. When administered i.p. with sheep red blood cells (SRBC), 5 to 100 micrograms of FB1 reduced the number of plaque-forming cells (PFC) produced against SRBC; however, when administered daily, 1 to 50 micrograms of FB1 caused a 4 to 12-fold increase in the number of PFC after SRBC injection. Therefore, FB1 is not only immunosuppressive; but also, immunostimulatory. To test the possibility that there may have been an immune response to FB1 as an antigen, FB1 was injected into mice and the number of splenic cells forming rosettes on FB1-treated SRBC was determined. There were dose-dependent increases in the antigen-binding cells, with up to 4.9- and 4.6-fold increases, respectively, upon primary and secondary immunization. FB1-binding immunoglobulins could be detected in sera from some treated mice, but this response was not obtained in every experiment. In summary, these results show that FB1 has diverse effects on the immune system, causing both stimulation and suppression of the response to foreign antigens, and apparently inducing an antigenic response to FB1.

Adjuvants, Immunologic↗
PubMed1991

Effects of CI-949, a novel antiallergy agent, on immune function of male Fischer 344 rats.

CI-949 is an orally effective inhibitor of allergic mediator release as measured with in vitro and animal models. To assess the effects of CI-949 on immune function, male Fischer 344 rats were evaluated for splenic T- and B-lymphocyte populations, antibody-forming cell response to sheep red blood cells (sRBC), concanavalin A- and pokeweed mitogen-induced lymphocyte proliferation, Natural Killer cell activity and reticuloendothelial system clearance of sRBC. CI-949 was administered by gavage to rats at 25, 50 and 100 mg/kg/day for 14 consecutive days. A vehicle control and two positive controls (cyclosporine A and cyclophosphamide) were run concurrently. CI-949 at 100 mg/kg/day decreased body weight gain and was lethal to 5 of 40 rats. The deaths occurred between days 5 and 12 of study. This overtly toxic dose did not alter splenic cellularity or change the percentages of T- and B-lymphocyte subpopulations. Additionally, CI-949 did not inhibit lymphocyte proliferation or hinder clearance of sRBC by the reticuloendothelial system. Antibody-forming cell response after immunization showed a dose-related increase in the number of immunoglobulin M secreting cells. Based on the results of these assays, the immune system does not appear to be adversely affected by CI-949 even at high doses.

Animals↗
PubMed2004

An investigation into the effect of a probiotic on gut immune function in surgical patients.

BACKGROUND: The gut-associated lymphoid tissue (GALT) is an important component of the gut barrier. We have previously demonstrated a significant increase in various parameters of gut immune function in association with bacterial translocation. Animal studies have suggested that the probiotic Lactobacillus plantarum 299v improves the immunological status of the intestinal mucosa. The aim of this study was to determine whether the same is true in humans. METHOD: This was a prospective randomised controlled study, in which immunohistochemical techniques were used to measure the concentrations of plasma cells, IgA positive cells and IgM positive cells in the lamina propria, together with the concentrations of IgA and IgM at the mucosal surface in specimens of normal small bowel obtained from patients undergoing elective abdominal surgery who had consumed an oral preparation containing the probiotic Lactobacillus plantarum 299v (ProViva) during the immediate preoperative period. These were compared with similar specimens obtained from control subjects who did not receive the probiotic. RESULTS: A total of 22 patients were studied (probiotic group n = 11, control group n = 11). The median volume of ProViva consumed was 3250 ml (range 2100-9000 ml), for a median duration of 9 days (range 5-18 days). There were no significant differences between the probiotic and control groups in terms of concentrations of plasma cells, IgA positive cells or IgM positive cells in the lamina propria. There was a significantly higher concentration of IgM at the mucosal surface in the control group (P = 0.02, Fishers Exact test mid P), but no difference in terms of IgA. CONCLUSIONS: The increase in IgA observed in the intestinal mucosa in response to probiotics in animal studies does not occur in humans. The significance of the increase in IgM at the mucosal surface in the controls is unclear.

Adult↗
PubMed1985

Effect of X-irradiation on epidermal immune function: decreased density and alloantigen-presenting capacity of Ia+ Langerhans cells and impaired production of epidermal cell-derived thymocyte activating factor (ETAF).

The mechanisms involved in the modulation of cutaneous immune responses by UV radiation have been extensively investigated; by contrast, few studies have addressed the effects of x-irradiation on epidermal immune function. We therefore investigated the effect of x-irradiation of mice on: (a) the density of epidermal Ia+ Langerhans cells (LC) in immunofluorescence studies, (b) epidermal cell (EC) allostimulatory capacity in the allogeneic EC-lymphocyte reaction (ELR), and (c) production of epidermal cell-derived thymocyte activating factor (ETAF). C3H/He and BALB/c mice were irradiated with 900, 1,800, 2,700, or 3,600 rad from a 137Cs source, and sacrificed 10 h or 3 days later. X-irradiation of mice 10 h previously only slightly decreased the density of epidermal Ia+ LC and did not affect the capacity of their EC to stimulate allogeneic responder lymphocytes in the ELR. X-irradiation of mice 3 days previously, however, resulted in a dose-dependent decrease in the density of Ia+ LC. This decrease was accompanied by a substantial reduction in EC allostimulatory capacity in the ELR at all doses of x-irradiation. ETAF production by cultured EC from mice x-irradiated 3 days previously was also found to be diminished at all doses of x-irradiation. Trypan blue exclusion studies demonstrated that the observed decreases in EC allostimulatory capacity and ETAF production were not the result of a generalized lethal effect of x-irradiation on EC. The reduction in EC allostimulatory capacity following in vivo x-irradiation could not be reversed by addition of exogenous ETAF or interleukin-1 in the ELR. Taken together, these results indicate that x-irradiation decreases the density of Ia+ LC, impairs LC alloantigen-presenting function, and reduces ETAF production. Thus cutaneous x-irradiation may affect inflammatory and neoplastic processes not only by its antimitotic activity, but also by a direct effect on EC which subserve immunologic functions.

Animals↗
PubMed2003

Effect of bisphenol A on murine immune function: modulation of interferon-gamma, IgG2a, and disease symptoms in NZB X NZW F1 mice.

To investigate the effects of the estrogen receptor-binding molecule bisphenol A (BPA) on murine immune function in vivo, we fed a low dose of 2.5 micro g BPA/kg body weight/day to both normal C57BL/6 and lupus-prone NZB X NZW F(1) (NZB/NZW) 5-week-old mice for 1 week. Analysis of concanavalin A (ConA)-stimulated splenic mononuclear cells by ELISA demonstrated that BPA-fed C57BL/6 males produced, on average, 40% less interferon-gamma (IFN-gamma; p < 0.01) and C57BL/6 females 28% less IFN-gamma (p < 0.05) compared with controls. Treated female NZB/NZW mice were monitored for lupus disease symptoms, defined as proteinuria (> 100 mg/dL albumin in urine for 2 consecutive weeks). Before the development of proteinuria, BPA-fed NZB/NZW mice produced significantly less ConA-stimulated IFN-gamma than did controls and displayed an average reduction of 50% in immunoglobulin G2a (IgG2a) antibody production from lipopolysaccharide (LPS)-stimulated splenocytes (p < 0.05). It is striking that 5-week-old female NZB/NZW mice fed a 7-day low-dose course of BPA developed proteinuria an average of 7 weeks later than did controls. Once proteinuria developed, splenocytes were stimulated with ConA for cytokine analysis. The BPA-fed mice showed a dramatic reduction of 64% in IFN-gamma production and a 32% reduction in ConA-stimulated interleukin-10 (p < 0.05). The long-lasting effects of BPA on IFN-gamma and IgG2a production likely contributed to the increased symptom-free period of the NZB/NZW mice.

Animals↗
PubMed1985

Deficient immune function of peripheral blood mononuclear cells from patients with Gardner syndrome.

Genetic susceptibility to certain cancers is recognized as a contributor to malignancy in man and experimental animals. Colorectal adenocarcinoma associated with Gardner syndrome is considered to be a hereditary form of cancer in which family members are at increased risk because they inherit an autosomal dominant gene for adenomas of the colorectum. The adenomas, if untreated, transform into adenocarcinoma. The purpose of the current study was to characterize immune function in patients with Gardner syndrome since reports exist of immune defects in patients with other forms of hereditary cancer. An analysis of the ability of lymphocytes from the patients to be stimulated by the T cell mitogens, phytohaemmaglutinin and concanavalin A, revealed severely depressed responses by peripheral blood mononuclear cells (PBMC) from all of the patients studied. A depressed response by patient PBMC to the B cell mitogen, pokeweed mitogen, also was observed but the extent of depression was not statistically significant. Natural killer (NK) cell activity of the patients was studied to determine if a possible genetic defect in this function is associated with Gardner syndrome. PBMC from half of the patients had marginally depressed NK cell function. An enumeration of patient cells revealed a significantly lower ratio of T4 (helper) to T8 (suppressor) T cells, but normal percentages of rosette forming, 7.2 (Ia) positive and Leu 11 positive (NK) cells.

Adolescent↗