Changes In Immune Parameters Research Articles

Anticipatory immune changes in women treated with chemotherapy for ovarian cancer

Immune parameters were assessed in 22 women before chemotherapy for ovarian cancer and compared with assessment made at home 2 days earlier. In the hospital, as compared to home measures, patients had a lower percentage of lymphocytes and monocytes and a higher percentage of granulocytes. Absolute numbers of lymphocytes were lower at the hospital as compared to at home. T-cell proliferative responses to concanavalin A were elevated for cells isolated from hospital blood samples as compared to home samples. The observed changes in immune parameters were not related to levels o r state anxiety at home or at the hospital. The results show anticipatory immune changes in a group of patients receiving chemotherapy that did not include cyclophosphamide.

Changes in the immune response of the ring dove ( Streptopelia risoria) during incubation

Changes in immune parameters following antigen administration were evaluated in non-breeding and incubating, male and female ring doves. The time course in the changes in immune parameters in response to antigen agrees closely with earlier studies on the domestic fowl. Incubating doves possessed phagocytes with increased activity, although there was no increase in cell number. These results suggest that in the incubating bird, with high levels of plasma prolactin, there is an antigen-independent increase in immune cell activity but no antigen-dependent action on cell number. The biological significance of the changes in the immune system during incubation awaits further study.

Age-related changes in immune parameters in a very old population of Swedish people: A longitudinal study

This study used a longitudinal design to examine age-related changes in a well-defined sample of Swedish people ranging from 86 to 92 years of age at baseline. The longitudinal design encompassed three measurement occasions with 1 year intermeasurement intervals. The results were analyzed by multivariate analyses of variance (MANOVA), which is useful for comparing individuals over time. Healthy middle-aged subjects (39 years SD ± 5.8) served as controls. The proliferative responses to Concanavalin A (Con A), a T-cell mitogen, indicated significant lower levels in responses of the old when the two groups were compared. The MANOVA revealed no significant change in mitogen responses over measurement occasions in the old sample as compared with the young. However, when cell types and lymphocyte subpopulations were examined, significant differences were found between the two age groups in many of these parameters and for some (lymphocyte percentages and numbers, CD3 numbers) the MANOVA indicated significant decreases over the measurement occasions in the very old. The results also consistently indicated significant intraindividual correlations in cell types, lymphocyte subpopulations, and mitogen responses over time.

Stress-Induced Changes in Immune Function Are Associated with Increased Production of an Interleukin-1-like Factor in Young Domestic Fowl

Investigation of the effects of stress on the immune system in young developing animals is hampered by many variables such as maternal interactions and physical size of immune organs. Young, precocial domestic fowl were used to overcome these difficulties. Domestic fowl, 14 days posthatch, served as an animal model to investigate the effects of stress (acute social isolation) on a rapidly developing immune system. Group-housed animals were isolated for 30, 60, or 90 min and assayed for numerative and functional changes in immune parameters in spleen and blood. The socially isolated birds showed an increase in body temperature, indicative of stress. The number of leukocytes/ml of blood increased in a time-dependent fashion, but the number of leukocytes in the spleen did not. The stress of isolation resulted in a significant increase in B-lymphocyte mitogen proliferation at 30 min, which decreased with time. Social stress also induced a time-dependent decrease in T-lymphocyte mitogen proliferation, which was significant by 90 min. Associated with changes in mitogen responsiveness was a significant increase in the production of an IL-1-like factor by splenic adherent cells from animals isolated for 30 min, which decreased in a time-dependent manner to return to baseline by 90 min. Thus, young domestic fowl represent a practical model for the examination of the effects of stress on immune function in a developing animal.

Immune changes in test animals during spaceflight.

Over the past two decades, it has become apparent that changes in immune parameters occur in cosmonauts and astronauts after spaceflight. Therefore, interest has been generated in the use of animal surrogates to better understand the nature and extent of these changes, the mechanism of these changes, and to allow the possible development of countermeasures. Among the changes noted in animals after spaceflight are alterations in lymphocytic blastogenesis, cytokine function, natural killer cell activity, and colony-stimulating factors. The nature and significance of spaceflight-induced changes in immune responses will be the focus of this review.

Acute exercises stress modulates immune function in unfit horses

Summary Since exercise stress is associated with multiple changes in immune parameters, we evaluated the effect of acute exercise on 3 indices of immune function in the horse. Six unconditioned thoroughbred horses were subjected to a tread- mill-based exercise challenge. Exerci se intensity was determined by monitoring each horse's heart rate, plasma lactate, and cortisol levels. Concurrently, peripheral blood mono- nuclear cells were used to assess pokeweed mitogen (PWM) -induced blastogenesis, influenza-specific proliferation, and lymphokine activated killer (LAK) cell activity. Heart rate peaked during the gallop on an incline while lactate was highest at the end of the stress test (To) with values of 200 bpm and 9 mM/L respectively. Average plasma cortisol was great- est at TO and T+2o with values 76% higher than unstressed horses. Significantly (P

Short and medium-term influence of physical activity on immune parameters.

Physical stress induces different changes in immune parameters depending on effort schedule and/or customary physical training. The mechanisms whereby they take place and the occurrence of possible tolerance after repeated effort have not been conclusively elucidated. We studied short and medium-term exercise-induced changes in immune parameters after a standard physical effort (24' of cycle ergometer up to the 80% of maximal heart rate, daily for 5 days) in a group of healthy untrained controls. White Blood Cells, lymphocyte subsets, plasmatic catecholamine and cortisol levels, IgG and IL2receptor (IL2R) levels were determined. Most of the observed changes were strictly acute effort-related and disappeared within 3 hours (except for shifts in CD4+ CD45RA+ and CD4+ CD45RA- lymphocytes): they were concomitant to a transient sympathetic activation proved by heart rate (HR) and Norepinephrine (NE) increase. The medium-term effects of repeated daily effort included only a questionable rise in CD19+ and CD3+ CD4- CD8- cells. As far as possible tolerance mechanisms are concerned, we did not detect any change in either the direction or the entity of effort-induced changes in our controls after repeated effort. Study of strictly standardized exercise protocols is mandatory before clinical applications of physical activity in the approach to the treatment of disimmune diseases.

Chronic effects of subcutaneous interleukin-2 therapy on soluble interleukin-2 receptors in advanced small cell lung cancer.

The increase in IL-2 receptor serum levels is one of the most typical changes in immune parameters during IL-2 cancer immunotherapy. To better define the effects of prolonged IL-2 injection on SIL-2R levels, we evaluated 7 advanced small cell lung cancer patients who received IL-2 subcutaneously at a daily dose of 9 x 10(6) IU/m2/12h for two days followed by 3 x 10(6) IU/m2/12h for 18 days (5 days/week for 4 weeks). Moreover, four patients were also evaluated during the second IL-2 cycle. Venous blood samples were drawn before and at weekly intervals during IL-2 therapy. Mean SIL-2R serum levels rapidly increased with the start of IL-2 injection, and they were significantly higher than the baseline levels throughout the immunotherapy cycle. The increase in mean SIL-2R levels was higher in patients with progressive disease than in those with response or stable disease, but the difference was not significant. Finally, the increase in mean SIL-2R concentrations during the second IL-2 cycle was not significantly different from that seen during the first one. The present study confirms that IL-2 administration determines an evident increase in SIL-2R levels; moreover, it would demonstrate that re-exposure to IL-2 after a rest period does not induce a more pronounced SIL-2R release.

Immunotoxicity of subchronic versus chronic exposure to aldicarb in mice

In this study we compared the immunotoxicity of subchronic vs chronic exposure to the aldicarb insecticide at a relatively low, 0.1 – 10 ppb, level in drinking water. The immunotoxicity of aldicarb was evaluated in 28- and 90-day studies by determination of the humoral, cellular and nonspecific immunity in inbred C57BL/6 mice. Quantification of splenic plaque-forming cells (PFC) to sheep erythrocytes (SRBC), mitogen activation of spleen lymphocytes, mixed lymphocyte reaction (MLR) and the cytofluorometric assay of the phagocytic uptake of fluorescent beads were among the parameters studied. Neither the cell viability nor the splenic cell count was affected by the insecticide exposure. Immunophenotyping and cytometric determination of L3T4 +, Lyt2 + and Ig + cells revealed no effect of the insecticide exposure on the total count of cell subsets in the ungated splenocyte population. However, a marked shift in the percentagesof L3T4 + and Lyt2 + cells was noted after subchronic exposure to 1 and 10 ppb aldicarb, possibly indicating activation of these splenic T-cell subsets. Subchronic aldicarb exposure significantly suppressed the splenic PFC response to SRBC at1 ppb dose, however, no dose—effect correlation could be concluded. Similarly, no dose—effect correlation was observed for subchronic aldicarb-related changes in mitogen responses. Subchronic exposure to aldicarb had no statistically significant effect on the mixed lymphocyte reaction (MLR) or on the macrophage phagocytosis. Chronic exposure to 0.1 – 10 ppb aldicarb did not affect any of the parameters measured, including the cell subsets. Thus, aldicarb-related changes in immune parameters, noted after a 28-day exposure, were compensated over chronic exposure to the insecticide.

RESPONSES OF LYMPHOCYTE SUBSETS, MITOGEN-STIMULATED CELL PROLIFERATION, AND IMMUNOGLOBULIN SYNTHESIS TO VIGOROUS EXERCISE IN WELL-TRAINED ATHLETES

Lymphocyte subsets, mitogen-stimulated cell proliferation rates, and immunoglobulin levels were evaluated before and following 30 min of treadmill exercise at 80% of directly measured maximal oxygen intake. The subjects were 10 well-trained male runners (age 29.8 ± 1.7 years, maximal oxygen intake 65.3 ± 4.9 ml kg−1 min−1, 10 km times 32:17 ± 1:38 min). The treadmill session induced a 20% increment of plasma cortisol 5 min following exercise, with restoration of normal values 30 min postexercise. High initial plasma creatine kinase levels showed a small increase 5 min postexercise, with a trend to a further increment 30 min postexercise. The percentages of T-lymphocytes and B-lymphocytes in peripheral venous blood were unchanged by exercise, but there was a decrease in the percentage of helper cells 5 min postexercise, with a trend to a small and transient decrease in the helper cell/suppressor cell ratio. The exercise session had no influence upon the proliferative response of peripheral blood mononuclear cells to mitogens, but there was a significant increase of pokeweed mitogen-stimulated IgG synthesis 5 min postexercise, with an incomplete return to normal values at 30 min. It may be concluded that 30 min of treadmill exercise comparable with a normal training run induces no more than transient changes of immune parameters in the well-trained distance runner.

Splenic immunomodulation with swimming-induced stress in rats

In order to determine the effects of swimming-induced stress, young male Wistar rats swam for a single session of 2 h duration, or for one 2-h session a day for five consecutive days. The absolute number of splenic mononuclear cells and the in vitro proliferation of mitogen-stimulated (PHA) T lymphocytes were studied. A single swimming session did not significantly diminish the number of splenic mononuclear cells, but it did significantly reduce splenic T-lymphocyte proliferation. This effect on T-lymphocyte proliferation was significantly blocked, in part, by subcutaneous injection of naltrexone before a swimming session. It was not significantly blocked by pre-exercise oral administration of aminoglutethimide. Repeated swimming sessions induced no significant changes in immune parameters. In conclusion, these data suggest that immunosuppression seen with a single swimming-induced stress period may partly be due to endogenous opioids, and that repetition of the swimming session reduced swimming-induced immunomodulation.

Immune Function in Growth Hormone‐Deficient Children Treated with Biosynthetic Growth Hormone

Conflicting data regarding the immune function in growth hormone (GH) -deficient children or changes in immune parameters during substitutive GH therapy have been reported. We have studied the immune function in 13 patients with GH deficiency before and during treatment with biosynthetic GH (12 IU/m2 body surface/week) after 6 and 12 months of therapy. We found that the absolute number of total T lymphocytes and T-cell subsets (using monoclonal Ab as markers), Natural Killer cell activity (target K562) and response of lymphocytes to polyclonal mitogens (PHA, ConA, PWM) were all in the normal range and remained so after 6 and 12 months of therapy. The absolute number of B lymphocytes was in the normal range before treatment and after 6 months of therapy but dropped significantly after 12 months of treatment. Serum immunoglobulins (IgG, IgA, IgM) did not show a parallel drop and remained normal throughout the whole study. Our GH-deficient patients did not show any undue susceptibility to infections and our data thus seem to confirm that the immune function is basically intact in these children and that it is not suppressed by GH treatment. Although a drop in B lymphocytes was observed, the normal level of immunoglobulins and the normal functional response to PWM seem to demonstrate the maintenance of a normal humoral immune response.

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Many autoimmune diseases are associated in Caucasians with HLA-B8 and/or HLA-DR3 antigens. There is evidence that bearers of these antigens may display significant changes in immune parameters when compared to individuals not having these antigens. Recently, increased numbers of blood activated T lymphocytes have been reported in the majority of these diseases. The increase in activated blood T lymphocytes is paradoxically characterized by an in vitro impairment of T cell activation. Particularly, an inadequate production of interleukins has been observed. We have studied blood levels of activated T cells in HLA-typed, healthy subjects. The results show that the percentage of activated T cells, as recognized by monoclonal antibodies anti-CD25, anti-Ia and anti-MLR3, was more frequent in HLA-B8, DR3 positive individuals. On the other hand, in the 24 h, PHA stimulated cultures IL-2, IFN-gamma and the percentage of T cells CD25 positive were decreased. Thus, there was an apparent discrepancy between the increase of blood activated T cells and the in vitro impaired T cell activation. Since there is evidence that HLA-B8, DR3 positive subjects are genetically low responders, a possible reason for the discrepancy might be their relative inability to remove antigenic stimuli from the body. In this case, the increased number of activated blood T cells may reflect a cellular activation caused by persistent antigenic stimulation.

The effects of irradiation on major histocampatibility complex expression and lymphocytic infiltration in the normal rat brain and the 9L gliosarcoma brain tumor model

The effects of irradiation on major histocompatibility complex (MHC) expression and lymphocytic infiltration in the normal rat brain and the 9L gliosarcoma brain tumor model were examined. Doses of irradiation administered were biologically equivalent to that used in the treatment of patients with malignant gliomas. No significant change in immune parameters was observed following irradiation in the normal rat brain. In the 9L gliosarcoma model irradiation did not suppress MHC expression or lymphocytic infiltration. These findings suggest that prior exposure to therapeutic irradiation need not adversely affect subsequent immunotherapies, and provide a foundation for future studies of immunomodulation in the irradiated brain.

HLA‐B8,DR3 PHENOTYPE AND LYMPHOCYTE RESPONSES TO PHYTOHAEMAGGLUTININ

Several reports have shown that HLA-B8,DR3 positive subjects may display some changes in immune parameters when compared with HLA-B8,DR3 negative ones and are prone to develop several immunological diseases. In the present study we have analysed the proliferative response to phytohaemagglutin (PHA) in HLA-typed healthy subjects. A twin method was also employed to assess the role of genetic and environmental factors in the regulation of the response to the mitogen. It was not possible to demonstrate any difference in proliferative response to optimal doses of PHA between groups of subjects carrying or not carrying the HLA-B8,DR3 phenotype. When suboptimal responses were studied, however, the results showed that lymphocyte responses were significantly decreased in HLA-B8,DR3 positive subjects compared with the negative ones. Moreover, the experiments performed with twins demonstrated that environmental factors were more important than genetic factors in the proliferative response to mitogen. The fact that the HLA-B8,DR3 phenotype affects the suboptimal response to PHA although environmental factors are more important than genetic factors in the response to the mitogen seems of some interest. However, these results could be consistent with the high incidence of autoimmune disorders among HLA-B8,DR3 positive individuals.

Immune function in growth hormone-deficient children treated with biosynthetic growth hormone.

. Conflicting data regarding the immune function in growth hormone (GH) -deficient children or changes in immune parameters during substitutive GH therapy have been reported. We have studied the immune function in 13 patients with GH deficiency before and during treatment with biosynthetic GH (12 IU/m2 body surface/week) after 6 and 12 months of therapy. We found that the absolute number of total T lymphocytes and T-cell subsets (using monoclonal Ab as markers), Natural Killer cell activity (target K562) and response of lymphocytes to polyclonal mitogens (PHA, ConA, PWM) were all in the normal range and remained so after 6 and 12 months of therapy. The absolute number of B lymphocytes was in the normal range before treatment and after 6 months of therapy but dropped significantly after 12 months of treatment. Serum immunoglobulins (IgG, IgA, IgM) did not show a parallel drop and remained normal throughout the whole study. Our GH-deficient patients did not show any undue susceptibility to infections and our data thus seem to confirm that the immune function is basically intact in these children and that it is not suppressed by GH treatment. Although a drop in B lymphocytes was observed, the normal level of immunoglobulins and the normal functional response to PWM seem to demonstrate the maintenance of a normal humoral immune response.

Serial immunological testing in patients with gastric cancer.

Standard immunological parameters measuring non-specific cellular immune reactivity were determined in 175 patients with different stages of gastric cancer prior to surgery and during follow-up. Several tests measuring monocyte activity were also employed. The total number of T cells and their subpopulations Ta and T29o was unchanged except depression of T29o in stage IV. The blastogenic response of lymphocytes to PHA as assessed by stimulation of protein synthesis was only depressed in stage IV. In contrast the PHA-induced lymphokine production was increased in all patients but the differences were significant for stage III and IV. Monocyte Fc receptor expression was increased in stages II-IV, while nitro blue tetrazolium reduction and antibody dependent cellular cytotoxicity of monocytes was elevated in stage IV. The number of extractable monocytes was not increased. Longitudinal studies suggested that most of the parameters normalized during follow-up. No major long-term impact of chemoimmunotherapy (5-FU + BCG) on the immune parameters was observed except a transient increase in PPD reactivity approximately 1 year after commencement of treatment. In patients with stage III gastric cancer the increased occurrence of suppressor cells (mostly monocytes) and elevated cytostatic activity of monocytes was associated with a longer survival while the increased lymphokine production and Fc receptor expression were seen in the group of patients succumbing earlier. We concluded that most of the changes in immune parameters were seen only in advanced disease and paradoxically disappeared in the course of disease. The determination of monocyte activity seems to be a sensitive indicator of immune system dearrangements in earlier stages of cancer and a useful prognostic factor in gastric cancer.

Early changes in immune parameters induced by an acute nonantigenic inflammation in mouse: Influence of imuthiol

Calcium pyrophosphate (CaPP)-induced pleurisy, may represent one of the simplest expressions of inflammation in that the irritant is a non-diffusible, non-antigenic and non-pyrogenic agent. Spleen or lymph node T or B cell numbers and activities, as well as NK activity, were modified at distance by CaPP-pleurisy. An intense increase in blood polymorphonuclear cells was also triggered by the inflammatory process. Treatment with imuthiol (sodium diethyldithiocarbamate), an agent known to be active on the T-cell lineage, restored towards control values the inflammatory response and tended to normalized white blood cell percentages altered by the inflammatory process. The findings suggest imuthiol could be employed as a virtually non-toxic and non-steroidal anti-inflammatory agent.

Changes in parameters of immunity in intact and partially hepatectomized mice after transplanation of spleen cells from hypokinetic donors

Changes in parameters of immunity in intact and partially hepatectomized mice after transplanation of spleen cells from hypokinetic donors

Correlation of Nonspecific Immune Monitoring with Rejection or Impaired Function of Renal Allografts

Two nonspecific immunological assays were combined with radionuclide scanning to monitor 113 patients thrice weekly following allotransplantation. The nonspecific immune assays included measurement of the percentage of active T rosette-forming cells (% A-T RFCs) and spontaneous blastogenesis (SB). An increase in SB and decrease in % A-T RFCs (greater than 1 sd of normal controls) constituted an immune event. The immune parameters were correlated with thrice weekly radionuclide studies which were computer analyzed for glomerular and tubular function. Alteration of the immunological and radionuclide parameters significantly correlated (P less than 0.001) with 90 rejection episodes displayed by 72 nonantithymocyte globulin (ATG)-treated renal allograft recipients during the first 30 postoperative days. In the absence of clinically defined rejection, changes in immune parameters correlated with (1) decline of radionuclide parameters and (2) alterations in weight, temperature, creatinine clearance, and serum creatinine, suggesting subclinical events. As a result of the effects of ATG on lymphocytes, a similar comparison could not be made for 41 other patients treated with this immunosuppressive drug. The incidence of false positive tests was 12.7%. Thus, the combination of two nonspecific immune parameters, % A-T RFCs and SB, with computerized analysis of radionuclide scans may afford a reliable index to diagnose early rejection or impaired function of renal allografts.