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[Enhancement of the therapeutic effect and red cell immune function by radix Trichosanthis in mice bearing Ehrlich ascites carcinoma].

Various red cell immune functions were determined in 60 mice bearing Ehrlich ascites carcinoma treated and untreated with Radix Trichosanthis(RT), and compared with these of 30 normal mice. In mice bearing Ehrlich ascites carcinoma treated with RT, the rosette formation of red cell C3b receptor, the rosette formation of red cell immune complex, the rosette formation rate of red cell round cancer, the rate of PMN phagocytosis were enhanced, and the activity of superoxide dismutase (SOD) was satisfactory higher than those in mice bearing Ehrlich ascites carcinoma untreated with RT, and almost same as those in normal mice, while the rosette inhibition rate of red cell C3b receptor in serum was satisfactory lower than that in mice bearing Ehrlich ascites carcinoma untreated with RT, and almost same as that in normal mice.

Animals

Humoral and cellular immune functions are not compromised by the anticarcinogenic Bowman-Birk inhibitor.

Previous studies have demonstrated that the soybean-derived Bowman-Birk protease inhibitor (BBI) is effective as a cancer chemopreventive agent in several animal model systems. Proteases represent a key component of several aspects of immune function; therefore the immune system is a primary target for potential toxicity. The present investigation examines the effect of dietary and intraperitoneally administered BBI on antibody response to keyhole limpet hemocyanin and delayed-type hypersensitivity response to dinitrochlorobenzene. Primary antibody response was not altered by BBI treatment; however, an elevated secondary response was observed in animals receiving dietary BBI at two weeks of age. This effect was not observed at later time points. No change in delayed-type hypersensitivity response was observed in any of the treatment groups.

Animals

Nutritional status, grip strength, and immune function in institutionalized elderly.

The effects of vitamin supplementation on grip strength and immune function was studied in a group of institutionalized elderly with a relatively higher prevalence of low and below acceptable biochemical parameters of vitamin C, pyridoxine, folic acid, riboflavin, iron and zinc nutriture. The vitamin supplementation has resulted in a statistically significant increase in the level of biochemical parameters related to added vitamins, and the number of subjects with inadequate vitamin values was reduced to zero. The improved vitamin status had a positive and statistically significant effect on the delayed cutaneous hypersensitivity one of the parameters of cellular immunity. The calculation of multiple correlation after inclusion of all biochemical parameters into the stepwise regression analysis has shown that the coefficient of multiple regression between examined biochemical parameters of nutrition status and delayed cutaneous hypersensitivity was R = .599 (p less than 0.001) which indicates that about 36% of the variability in the cellular immunity would be affected by the vitamin and mineral nutrition status.

Aged

Photoperiod and population density interact to affect reproductive and immune function in male prairie voles.

Seasonal breeding of rodents is often associated with changes in adrenal function; altered adrenal function could account, in part, for seasonal changes in immune function and, ultimately, influence seasonal fluctuations in survival. Animals commonly monitor the annual change in photoperiod to ascertain the time of year and to make appropriate seasonal adjustments in physiology and behavior. Several extrinsic factors affect reproductive responsiveness to photoperiod. The interaction between population density and reproductive and adrenal responsiveness to photoperiod was assessed in the present experiment. Adult male prairie voles (Microtus ochrogaster) were maintained individually for 10 wk in long [light:dark (LD) 16:8] or short (LD 8:16) photoperiods in rooms with either high (10.96 animals/m3) or low (0.18 animals/m3) population densities. Regardless of population density, short-day voles regressed the size of their reproductive organs; reproductive organ masses were higher in long-day voles housed in high-density compared with low-density rooms. Paired adrenal masses were reduced in short-day voles, but were unaffected by population density; serum corticosterone concentrations were significantly elevated in short-day compared with long-day animals. In both photoperiods, basal blood corticosterone levels were higher in voles from low-density compared with high-density rooms. Splenic masses were unaffected by day length, but were elevated among high-density animals. Similarly, serum immunoglobulin (IgG) levels were elevated among high-density animals. These results suggest that population density per se, in the absence of behavioral interactions, can affect reproductive size, and possibly function, in long-day conditions, and that prairie voles, which are highly social, exhibit higher corticosterone and lower IgG levels in low compared with high densities. These results may be important in understanding arvicoline population fluctuations, as well as improving animal husbandry practices in the lab.

Animals

Stimulatory effects of FK156 in a panel of tests designed to detect changes in immune function.

There is a need to evaluate the utility of experimental models in immune function assessment if these are to be accepted in preclinical safety studies. We have evaluated a panel of tests measuring cellularity and functions of the lymphoid system in the Fischer rat in order to determine whether they would detect immunostimulation, rather than suppression. Injection of the peptide immunostimulant FK156 (D-lactyl-L-alanyl-y-D-glutamyl-(L)-meso-diaminopimelyl- (L)-glycine) increased the numbers of macrophages recovered from the peritoneal cavity, and stimulated their activity, as measured by chemiluminescence, adherence, and secretion of interleukin 1. In vitro, T lymphocytes had an increased background incorporation of tritiated thymidine, increased response to sub-optimal concentrations of concanavalin A, and an increase in secretion of interleukin 2 at optimal concentrations of concanavalin A. There was no change in the proliferative responses of B lymphocytes in vitro. Antibody responses to tetanus toxoid in vivo were increased. These changes were not reflected in consistent, statistically significant alterations in the numbers of lymphocytes bearing either lineage markers or the interleukin 2 receptor as a marker of activation.

Adjuvants, Immunologic

Stressor-induced alterations of immune function: mechanisms and issues.

This paper reviews the role of catecholamines and the hypothalamic-pituitary-adrenal system in the mediation of stress-induced immune changes in both human and animal subjects. There is evidence to support the importance of these factors in mediating stressor effects on certain immune parameters, but further research is needed to define the specific circumstances in which they are relevant. Therefore, discussion of such issues as sex, genotype, stress history, environment, and stressor characteristics is provided to suggest possible ways to increase our understanding of stressor effects on immune function. Since the imposition of a stressor disrupts physiological homeostasis, understanding the capacity of the immune system to function under such conditions is of prime importance in predicting disease onset and outcome.

Animals

Nutrition and immune function.

Despite provision of adequate calories and nitrogen, patients receiving current nutrition support formulations often have suppression of immune function. Certain nutrients may act pharmacologically on the immune system. The choice of nutrients appropriate for a given disease state must take into consideration the nutritional status of the subject, presence of infection, injury or hypermetabolism, and the specific immune defect. Nutritional therapy specific for certain disease states is complex and in its infancy but may hold promise for improved patient outcome. Randomized prospective trials to evaluate efficacy are mandatory. Continued research into individual nutrients to elucidate mechanisms of immunomodulation must follow. In the meantime, broad application of products shown to be effective for a specific indication is inappropriate.

Enteral Nutrition

Long-term effect of postoperative irradiation on the immune functions in patients with mammary carcinoma.

The effect of postoperative irradiation on the immune functions of 13 patients with breast carcinoma is reported, using as parameters the peripheral blood lymphocyte count, percentages of E and EAC rosette forming cells, and lymphocyte proliferative responses to PHA, Con A and PPD. After irradiation the number of peripheral blood lymphocytes was reduced during 8 months. The percentages of E and EAC rosette forming cells were not altered during the observation time of 7 to 36 months. In the proliferative responses of lymphocytes to PHA, Con A and PPD, the postoperative irradiation caused a decrease which, regarding PHA and Con A, lasted up to 8 months and then recovered. The decrease in the proliferative responses to PPD was stronger and lasted during the whole observation time. In the mitogenic responses of patients with recurrent or disseminating disease no difference could be demonstrated as compared with the patients living recurrence-free.

Adult

Does fluoridation harm immune function?

There have been suggestions, mainly in the lay press, that fluoridation might affect immunity. Careful examination of various studies on fluoride and immune function do not support this suggestion. Whilst fluoride at high concentrations can have inhibitory effects on lymphocyte and polymorphonuclear leucocyte function, these concentrations are many times higher than levels which would be expected from fluoridation. Fluoride can act as an immunological adjuvant. There is no evidence of any deleterious effect on specific immunity following fluoridation nor any confirmed reports of allergic reactions.

Adjuvants, Immunologic

Effects of supplemental dietary arginine, canola oil, and trace elements on cellular immune function in critically injured patients.

Dietary nutrients may have pharmacological value in modulating the immune system. We studied the effects of two enteral diets, which differed in their content of arginine, fat source, and select trace elements, on immune function in critically injured patients. Leukocytes were isolated from healthy volunteers and severely injured (ISS > 13) patients on the first, sixth, and tenth day of receiving either a standard diet or experimental diet. Monocytes were assayed for tumor necrosis factor, procoagulant activity, and prostaglandin E2 following endotoxin exposure. Neutrophil oxidant production and lymphocyte blastogenesis was assessed. Leukocyte function was uniformly depressed compared to normal patients on day 1. The response of leukocytes from patients receiving experimental diet improved or "normalized" by day 6, while remaining depressed in patients receiving standard diet. Dietary nutrient modification can effect cellular immune responses to inflammatory stimuli in severely injured patients.

Adolescent

Soluble extracts from larval Ostertagia ostertagi modulating immune function.

BALB/c mice were immunized with Ostertagia ostertagi antigens and keyhole limpet hemocyanin (KLH) or sheep erythrocytes (SR) for evaluation of antibody production by enzyme linked immunosorbent assay (ELISA) or modified Jerne plaque assay. One semi-purified larval antigen caused both decreased anti-KLH serum antibody levels and fewer anti-SR IgM-secreting B cells. This antigen was shown to depress lymphocyte blastogenesis to Concanavalin A when added to cultured BALB/c splenic lymphocytes.

Animals

The effects of ultraviolet irradiation of the skin on herpes simplex virus infection: alteration in immune function mediated by epidermal cells and in the course of infection.

Previously, we demonstrated that Ia+ epidermal cells (EC) have herpes simplex virus (HSV) antigen-presenting capacity in vitro and play an important role in resistance to HSV infection in vivo. In the present study, we investigated the effects of in vivo ultraviolet (UV) irradiation of the skin on the HSV-immunity function of EC both in vitro and in vivo and on the pathogenesis of HSV infection. Immune T cells cultured with EC and HSV antigen showed a proliferative response in vitro. Exposure of the skin to UV light 1 to 3 days before preparation of EC resulted in dose-dependent impairment of this proliferation. This UV-induced impairment of the accessory cell function of EC was accompanied by a parallel reduction of the number of Ia+ EC. We also transferred these EC-stimulated T cells to intracutaneously infected nude mice. Immune T cells stimulated with EC obtained from irradiated mice did not effectively clear HSV and allowed development of zosteriform skin lesions. In contrast normal-EC-stimulated immune T cells completely prevented the formation of a zosteriform rash. In addition, mice irradiated with UV on shaved midflank skin 2 days before intracutaneous inoculation of HSV showed increased severity of infection and a higher incidence of latency compared with control mice. These studies indicate that in vivo UV irradiation of the skin abrogates the immune function of EC both in vitro and in vivo, and affects HSV pathogenesis. The implication of our results for the better understanding of the effect of UV on acute and recurrent HSV infections is discussed.

Animals

Effects of rat cytomegalovirus infection on immune functions in rats with collagen induced arthritis.

The effect of rat cytomegalovirus (CMV) infection on immune function was studied in rats with collagen induced arthritis, an experimental model of autoimmunity targeted to cartilage and previously shown to be greatly augmented in severity by rat CMV. Rat CMV infection induced an early (7 to 14 day), 2.5-fold increase in circulating B cells (SIgG+) which was associated with moderate increases in the titers of serum IgG antirat type II collagen antibody. A significantly increased skin test reactivity (p less than 0.025) to rat type II collagen was detected at Day 14 and followed a small increase in numbers of W3/25+ T-helper cells in peripheral blood noted at Day 8. A 3-fold expansion of OX8+ peripheral lymphocytes, occurring maximally at Day 8, was tentatively identified as a natural killer cell population by functional 51Cr-release assays. Our data indicate that rat CMV augmentation of collagen induced arthritis is associated with a generalized but modest increase in immune reactivity towards rat type II collagen and with significant alterations of peripheral lymphocyte subsets.

Animals

Immune function in the malnourished host.

Deficiencies of protein, energy, and specific vitamins and minerals impair function of various components of the immunological network and therefore weaken host defense. These various deficiencies may affect specific loci within the network, but because of the interrelations between the different systems, the ultimate effect may be quite broad. Patients with PEM often suffer infections, which may also impair the immune function. It is difficult to separate effects of malnutrition from those of infection, a fact recognized in the recent coinage of the term malnutrition-infection complex. On the basis of the available information it appears that PEM and associated deficiencies of nutrients cause a major impairment in the T lymphocytes and the complement system. They have relatively less effect on the B lymphocytes and the phagocytes directly; however, normal B cell activity is dependent on regulatory influences of T cells and the phagocytic cells require mediators generated from the activation of complement. Therefore these cells also are functionally defective in PEM. The consequence of these deficiencies of function of the immune system in the malnourished host is heightened susceptibility to and a less vigorous response to infections. These defects can be generally reversed by nutritional rehabilitation.

Antibody Formation

Thymus-dependent immune functions in chickens bursectomized with colchicine applied to the anal lips.

Thymus-dependent immune functions were investigated in chickens bursectomized neonatally with colchicine solution given per anum. Antibody responses to thymus-dependent antigens sheep red blood cells (SRBC) and human gamma-globulin (HGG) were delayed, reaching the normal level after the third antigen stimulation. Also the mitogenic responses of peripheral blood lymphocytes were preserved, and no changes in the thymic morphology were found. In contrast, antibody responses to bursa-dependent antigen Brucella abortus were low and the switch of immunoglobulin isotypes from IgM to IgA and IgG was disturbed. It can be concluded that neonatal bursectomy with cloacal administration of colchicine does not significantly affect T cell functions, whereas B cell functions are partially deficient.

Animals

In vivo and in vitro effects of 1,1-dimethylhydrazine on selected immune functions.

The in vivo phase of the experiments reported here include the evaluation of immune function after short-or long-term treatment of mice with 1,1-dimethylhydrazine (UDMH). Long-term exposure (3 injections/week for 14 weeks) resulted in increased numbers of Jerne plaque-forming cells, a trend toward decreased induction of suppressor cell activity by concanavalin A (Con A), and no effects on mitogen-induced lymphocyte blast transformation (LBT), compared to saline-treated control mice. These effects were greatest at doses of 10 or 50 mg/kg, while higher doses had less of an effect. In vitro experiments were performed by adding UDMH to normal murine splenocytes in the LBT assay and con A-induced suppressor cell assay. The UDMH induced a significant enhanced response to lipopolysaccharide (LPS) at 10 and 50 micrograms/ml, and a suppressed response to both Con A and LPS at higher concentrations. The UDMH also caused a decrease in suppressor cell activity at 25 micrograms/ml. Selective abrogation of suppressor activity or alteration of the suppressor cell-helper ratio were suggested as possible mechanisms for the enhancement effect associated with UDMH.

Animals

In vitro evidence for defective afferent immune function in long-term renal allograft recipients.

Experiments were designed to evaluate afferent immune functions in 21 long-term (greater than or equal to 3 years) renal allograft recipients by using in vitro assays that included autologous and allogeneic mixed lymphocyte reactions (AMLR and allo-MLR), proliferative responses to a soluble antigen (tetanus toxoid), and the ability to generate cytotoxic T lymphocytes (CTL) following stimulation in an AMLR. The results showed that allograft recipients generated responses in the allo-MLR (means = 84,789 +/- 8242) that were comparable to those exhibited by normal controls (means = 86,082 +/- 7423). Likewise, mean responses in the AMLR were similar in recipients and controls (14,937 +/- 3243 versus 16,101 +/- 3005), although a greater percentage of recipients generated AMLRs below 5000 cpm than did normals (8/21 versus 4/20). However, 13 recipients analyzed for responsiveness to tetanus toxoid were shown to generate mean proliferative responses that were significantly depressed below normal (18,095 +/- 5545 versus 48,935 +/- 8813, P less than 0.001). Furthermore, despite significant proliferation in the AMLR means = 27,648 +/- 5168), 8 recipients generated significantly lower CTL activity in AMLR cultures than normal controls (mean percentage of cytotoxicity = 10.3 +/- 4.7 versus 24.9 +/- 4.7, P less than 0.05). These recipients generated normal CTL levels against allogeneic target cells following stimulation in an allo-MLR. Thus, these studies provide experimental support for the existence of altered T helper cell-mediated functions in long-term renal allograft recipients.

Humans

Cellular immune functions, endorphins, and alcohol consumption in males.

The effects of alcohol abuse on cellular immune functions were measured by various levels of alcohol use in adult men. Total lifelong abstainers were used as controls. Previous abusers, current abusers, and patients with alcoholic cirrhosis or pancreatitis were age-matched to controls. T-lymphocyte mitogenesis stimulated by phytohemagglutinin and concanavalin A was generally reduced in peripheral blood lymphocytes of current and previous alcohol consumers, although the decrease was not statistically significant. B-cell mitogenesis stimulated by pokeweed mitogen was not changed by previous alcohol consumption. The number of T-cells was not changed by either previous or current alcohol abuse. T-helper cells were significantly increased and T-suppressor cells increased only in the patients with alcoholic cirrhosis or pancreatitis. The percentage of T-lymphocytes with T-suppressor characteristics in controls was 27% while in alcoholic cirrhosis or pancreatitis subjects it was 16%. Plasma corticosteroid levels were significantly increased in people currently consuming alcohol (12.1 +/- 1.1 mg/dl) compared to controls (7.7 +/- 1.1). The corticosteroid levels were also higher in previous alcohol abusers although not statistically significant. Plasma endorphin levels were increased by severe alcohol abuse in the patients with cirrhosis or pancreatitis to 25.03 +/- 6.74 from 11.85 +/- 2.48 pg/ml in controls.

Adult