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L Hoffman-Goetz

Publications and source records attributed to L Hoffman-Goetz.

At least 55 records · Page 3Linked to original sources

Effect of environmental enrichment and housing density on immune system reactivity to acute exercise stress.

Positive stress has been described in the literature but not well characterized experimentally. This experiment was designed to test the hypothesis that environmental enrichment and housing density in C57BL/6 female mice modulate immune responses to acute exercise stress. A 2 x 2 x 2 factorial design was used where enrichment (enrich), nonenriched (nonenrich), group housed (group), individually housed (ind), and stress (stress) or no stress (nonstress) acted as the independent variables. Enrichment involved a 7-week exposure to in-cage running wheels and a variety of cage objects. Ninety minutes after treadmill exercise stress at 25 m/min, 4 degrees slope, for 30 min (or no exercise stress) mice were sacrificed, and splenocyte blastogenesis to the T-cell mitogen concanavalin A (Con A), splenic T-cell subset enumeration, and percent live/dead splenic cells by flow cytometry were evaluated. Results showed significant interaction effects for mitogen responses, percent Ly2+ subset, and percent live/dead splenocyte responses. Proliferation to Con A was higher in nonenrich group-housed animals than other groups. Percent live/dead cell analysis revealed a significant housing x stress interaction with fewer percent live and higher percent metabolically stressed splenocytes obtained from ind-stressed mice than other groups. These data suggest that enrichment and housing density are important factors influencing immune responses in the basal state, and in response to exercise stress.

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Effects of different weight loss treatments on weight cycling and metabolic measures in male mice.

The effects of different weight loss treatments on subsequent weight regain, food efficiency, body composition, metabolic rate, and corticosterone concentrations were investigated in obese male B6D2F1 mice. Treatment groups were: restricted (RES, food restricted); exercised (EX, treadmill exercised); sham control (SHAM, treadmill exposure, not exercised); lab chow control (LC). Weight loss, regardless of treatment, resulted in increased rate of weight regain and food efficiency. There were significant alterations in body composition after a cycle of weight gain/loss. These results demonstrate that a cycle of weight gain/loss causes increased food efficiency and concomitant alterations in body composition in male mice.

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Exercise and the immune system: a model of the stress response?

Exercise influences natural immunity, T- and B-cell functions, and cytokine responses, through circulatory (hemodynamic) changes and by endocrine hormones secreted in response to physical stress. The magnitude of the effects on the immune system reflects the intensity, duration and chronicity of the exercise. In this review, Laurie Hoffman-Goetz and Bente Klarlund Pedersen suggest that exercise-immune interactions can be viewed as a subset of stress immunology.

B-Lymphocytes↗

Exercise and breast cancer: review and critical analysis of the literature.

Breast cancer is one of the leading causes of cancer and cancer mortality among Canadian women. Based on the current incidence rates, the National Cancer Institute of Canada has estimated that one in 10 women will develop breast cancer during her lifetime. In an effort to control this disease, various prevention strategies have been proposed. One promising strategy involves the promotion of exercise in healthy women. It has been hypothesized that exercise may protect against breast cancer by influencing regularity of ovulatory cycles, by changing body fat composition, or by enhancing natural immunity. In this paper both the epidemiological and experimental evidence that speaks to a protective effect of exercise is reviewed. Although there are several biologically plausible mechanisms for the association, the existing epidemiological and experimental data are inconclusive due to the small number of studies and their methodological insufficiencies. However, given the enormous potential benefit of even a small protective effect of exercise, further studies designed to address the relationship between exercise and breast cancer risk are warranted.

Adult↗

Exercise, natural immunity, and tumor metastasis.

Exercise has been shown to reduce the growth of primary tumors and to enhance certain aspects of host natural immunity. The question of whether these are independent phenomena or are casually related has not been systematically evaluated. This paper presents information concerning the methodological difficulties in studying proposed relationships between exercise and cancer, focusing specifically on tumor metastasis, the process by which malignant cells disseminate to distant organs and establish new colonies. This paper also focuses on how natural immune processes and tumor cells exert bidirectional influences on each other. It is suggested that the direction of the impact of exercise on the control of metastatic spread of neoplastic cells will reflect, in part, the sensitivity of the specific tumor to cytolysis by natural immune mechanisms, the route of dissemination, the timing of exercise relative to tumor exposure, and whether exercise acts as a distress or eustress state.

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Lymphokine activated killer cell activity following voluntary physical activity in mice.

The effect of eight weeks of voluntary wheel running exercise in female, outbred Swiss Webster mice on baseline splenic natural killer (NK) cell and interleukin-2 stimulated lymphokine activated killer (LAK) cell activity was studied. NK cell cytolytic activity against YAC-1 tumour targets was measured using a 51Cr release assay at the completion of a wheel running episode (end of dark cycle) or at 96 h after cessation of wheel running. LAK cell activity against tumour targets was generated from splenic NK cells by in vitro stimulation for 3 days with recombinant interleukin-2 (rIL-2). Wheel running was not associated with increases in baseline NK cytolytic activity either when sampled as a training effect (96 h after exercise) or immediately after exercise. Following an episode of wheel running exercise, LAK activity was significantly higher in the physically active compared to sedentary animals. These results support the concept that spontaneous wheel running activity enhances lymphokine activated killer cell activity following a cycle of active running; whether this greater LAK activity involves changes in IL-1, IL-2, or other cytokine concentrations or in the expression of IL-2 receptors on NK/LAK cells after exercise warrants further investigation. Given the clinical use of IL-2 to stimulate LAK cells in adoptive immunotherapy, it is possible (although untested) that exercise may have a potentially beneficial role as a treatment modality for some human cancers.

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Chronic exercise enhances in vivo and in vitro cytotoxic mechanisms of natural immunity in mice.

This study investigated the influence of 9 wk of chronic exercise on natural cytotoxicity in male C3H mice. Both in vivo cytotoxicity (pulmonary vasculature) and in vitro cytotoxicity (spleen) were determined for voluntary (wheel running; n = 30) and forced (treadmill running, 15 m/min, 30 min/day; n = 30) exercise protocols. A sedentary control group (n = 30) and a treadmill control group (5 m/min, 5 min/day; n = 30) were also included. After 9 wk of chronic exercise, submaximal exercise O2 uptake was reduced in the wheel-running group relative to that in sedentary or treadmill-trained mice. Maximal citrate synthase activity of soleus muscle was higher in treadmill-trained group compared with that in sedentary or wheel-running mice. Chronic exercise consistently reduced percent retention of CIRAS 3 tumor cells in the lungs of treadmill- (15.3 +/- 1.4) and wheel- (17.9 +/- 1.4) trained mice below that of sedentary (29.5 +/- 2.7) and treadmill control (25.8 +/- 1.8) groups (P < 0.001). Injection of anti-asialo GM1 (ASGM1) antibody increased tumor cell retention in the lungs for all groups but did not alter the differences between activity conditions. In vitro cytotoxicity was enhanced in treadmill- and wheel-trained mice relative to that in sedentary controls but was not elevated in the treadmill control group. Anti-ASGM1 injection eliminated in vitro cytotoxicity for all groups. Chronic exercise slightly increased the frequency of ASGM1-positive splenocytes in treadmill-trained mice only. These results indicate that chronic exercise enhances natural cytotoxic mechanisms in vivo and in vitro and that this enhancement is present for both forced and voluntary exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

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Effect of exercise on natural cytotoxicity and pulmonary tumor metastases in mice.

Exercise has been demonstrated to reduce experimental tumor formation in rodents when the exercise is present during the tumor initiation or promotion phases. This study evaluated whether exercise influenced the process of tumor metastasis and subsequent growth in a secondary implant site. Male C3H mice remained sedentary, were given free access to running wheels, ran on a treadmill (15 m.min-1, 30 min.d-1), or walked on a treadmill (5 m.min-1, 5 min.d-1)(N = 20/group). Following 9 wk of this protocol, exercise was discontinued. At this time all animals received a tumor cell dose (CIRAS 1, 3 x 10(5)) i.v., and remained sedentary until sacrificed 3 wk later. Splenic natural killer (NK) cell activity was elevated in the wheel running mice compared with sedentary controls 3 wk after cessation of exercise (F(3,74) = 6.266, P < 0.002). Exercised mice displayed lower tumor cell retention in the lungs relative to nonexercised mice (F(1,37) = 6.593, P < 0.02). Tumor incidence was not different across activity groups whereas tumor multiplicity was higher in mice that had been previously exposed to exercise. (However, it should be noted that the significant exercise-tumor effect was due to a small number of exercised mice with extreme multiplicity, > 200 foci/lung.) More extensive tumor colony formation was present in wheel-trained mice that displayed the greatest volumes of daily running. The results from this study suggest that exercise was able to augment natural immune cytotoxic function for up to 3 wk after cessation of activity. However, this augmentation of natural immune function was not associated with reduced tumor incidence in the exercised animals.

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Differential effects of exercise and housing condition on murine natural killer cell activity and tumor growth.

Acute exercise and exercise conditioning have been shown to affect the activity of natural killer (NK) cells as well as the growth of experimentally induced tumors in animals. Since psychosocial factors are also known to alter NK activity and tumor growth, isolation, a known psychosocial stressor of mice, was also investigated to see if housing condition could alter exercise-induced changes in NK cell activity and tumor growth. NK cell activity and concentration of asialo GM1 (ASGM1) positive splenocytes were measured in male C3H mice inoculated i.v. with CIRAS 3 tumor cells. Mice were housed individually or in groups of four and trained to run for eight weeks on a rodent treadmill; controls remained sedentary throughout the experimental period. At four weeks into the training protocol, mice were injected with the tumor cells and continued to run for four weeks after tumor exposure. There was a significant effect of physical activity (p less than 0.019) but not of housing on splenic NK cytotoxicity against tumor targets in vitro. When the data were analyzed by presence or absence of lung metastases, only those animals without visible lung tumors had significantly higher NK activity as a function of exercise relative to sedentary controls. There were no significant differences in the frequency of ASGM1+ splenocytes between trained and untrained animals, irrespective of presence or absence of lung tumor colonies. There was a significant effect of housing (p less than 0.02), but not of physical activity, in mice with successful tumor takes with greater numbers of group housed animals (29/59) with tumor relative to individually housed animals (13/60).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Effect of differential housing in mice on natural killer cell activity, tumor growth, and plasma corticosterone.

Various forms of stress have been shown to alter natural killer (NK) cell activity and tumorigenesis; however, few studies have measured these two variables simultaneously. Isolation of mice was utilized as a model of stress by which to study NK cell activity and pulmonary metastatic response following a tumor challenge. Male C3H mice were group or individually housed for 3 weeks, after which CIRAS 3 fibrosarcoma tumor cells or the tumor vehicle was injected intravenously (tail vein), NK cell activity, pulmonary metastasis, and plasma corticosterone were measured 1, 7, and 21 days following tumor cell inoculation. Individually housed mice, irrespective of tumor or vehicle condition, had a higher NK response on Day 1 relative to group-housed animals (P less than 0.001). By Day 21, tumor condition, rather than housing, was the major significant factor affecting NK activity (P less than 0.001). Nevertheless, individually housed, tumor-injected mice still had higher NK activity compared with the other treatment groups on Day 21. No effect of housing condition was present for the incidence of pulmonary metastases or frequency of metastases in affected animals. Plasma corticosterone levels generally increased over the study period, with no housing or injection effects at Days 1 and 7. Individually housed, vehicle-injected mice had higher corticosterone levels at Day 21 (P less than 0.01). These data suggest that in response to housing condition, NK cell activity differs in tumor-bearing mice and vehicle controls. Furthermore, CIRAS 3 pulmonary tumor formation is not affected by differences in NK activity consequent to housing condition. Plasma corticosterone does not appear to be a major in vivo regulator of NK activity in this experimental tumor system. Finally, the interpretation of housing effects on NK activity and plasma corticosterone levels depends on the temporal window in which sampling occurs.

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Effects of treadmill exercise on weight cycling in female mice.

Weight cycling increases food efficiency and rate of weight regain. This study induced weight loss in adult female B6D2F1 mice via dietary energy restriction and exercise to determine whether the weight loss regimen influenced rate of weight regain. Four groups of animals were studied: RES, restricted (food restricted); EX, exercised (treadmill exercised); SC, sham control (treadmill exposure, not exercised); LC, lab chow control (appropriately aged control). Both EX and SC voluntarily reduced food intake to the level of the RES animals. The RES group showed increased food efficiency and rate of weight regain relative to the LC group; this effect was attenuated in both the EX and SC groups. These findings demonstrate that a) the cycling phenomenon occurs in mice, and b) stressors such as forced exercise or exposure to a novel environment can modify the pattern of food efficiency and rate of weight regain engendered by dietary restriction.

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Impact of changes in housing condition on mouse natural killer cell activity.

Various psychosocial stressors, such as housing condition and rotation, have been reported to influence tumour growth. This study assessed the influence of housing condition and change in housing condition on natural killer (NK) cell activity, an important component of natural immune defense against cancer. Mice which were individually housed for four weeks did not differ from group-housed mice in NK cell cytolytic activity against tumour targets in vitro or in the frequency of NK cells in the spleen. Switching of housing condition (group to individual, individual to group) for one week did not change the splenic NK cytolytic capacity relative to mice which were not switched. The two groups of mice which experienced a change in housing condition were, however, significantly different from each other. These data suggest that an acute change in housing condition, rather than the housing condition per se, has differential effects on the capacity to kill tumours by NK cells.

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Lymphocyte proliferation responses after exercise in men: fitness, intensity, and duration effects.

This study investigated the effects of intensity and duration of exercise on lymphocyte proliferation as a measure of immunologic function in men of defined fitness. Three fitness groups--low [maximal O2 uptake (VO2max) = 44.9 +/- 1.5 ml O2.kg-1.min-1 and sedentary], moderate (VO2max = 55.2 +/- 1.6 ml O2.kg-1.min-1 and recreationally active), and high (VO2max = 63.3 +/- 1.8 ml O2.kg-1.min-1 and endurance trained)--and a mixed control group (VO2max = 52.4 +/- 2.3 ml O2.kg-1.min-1) participated in the study. Subjects completed four randomly ordered cycle ergometer rides: ride 1, 30 min at 65% VO2max; ride 2, 60 min at 30% VO2max; ride 3, 60 min at 75% VO2max; and ride 4, 120 min at 65% VO2max. Blood samples were obtained at various times before and after the exercise sessions. Lymphocyte responses to the T cell mitogen concanavalin A were determined at each sample time through the incorporation of radiolabeled thymidine [( 3H]TdR). Despite differences in resting levels of [3H]TdR uptake, a consistent depression in mitogenesis was present 2 h after an exercise bout in all fitness groups. The magnitude of the reduction in T cell mitogenesis was not affected by an increase in exercise duration. A trend toward greater reduction was present in the highly fit group when exercise intensity was increased. The reduction in lymphocyte proliferation to the concanavalin A mitogen after exercise was a short-term phenomenon with recovery to resting (preexercise) values 24 h after cessation of the work bout. These data suggest that single sessions of submaximal exercise transiently reduce lymphocyte function in men and that this effect occurs irrespective of subject fitness level.

Adult↗

Lymphocyte subset responses to repeated submaximal exercise in men.

The effects of repeated bouts of submaximal cycle ergometry exercise on changes in the percentage of peripheral blood T-lymphocytes, the T-helper/inducer and T-cytotoxic/suppressor subsets, and natural killer (NK) cells were studied in 18 healthy young men who had no history of regular exercise training. Subjects were matched on the basis of maximal O2 uptake and assigned randomly to exercise or control groups, with controls resting quietly during the exercise sessions. The percentage of peripheral blood mononuclear leukocytes that reacted with monoclonal antibodies specific for T-lymphocytes (CD3+ cells), the helper/inducer subset (CD4+ cells) and cytotoxic/suppressor subset (CD8+ cells) of T-lymphocytes, and cells with NK activity (Leu7+ cells) were enumerated by fluorescence-activated flow cytometry for samples obtained immediately before and after exercise on days 1, 3, and 5 of a 5-day exercise regimen. The results of this study were mixed with decreases in the percentage of T-lymphocytes before vs. after exercise on days 1 and 3 (P less than 0.001), a decrease in the percentage of T-helper/inducer cells before vs. after exercise on day 3 (P less than 0.05), no effect of exercise on the percentage of T-cytotoxic/suppressor cells, and a marked increase in the percentage of NK cells after exercise on days 1 (P less than 0.05) and 3 (P less than 0.01). The total number of recovered NK cells in the mononuclear leukocyte fraction of blood also increased significantly after exercise on days 1 (P less than 0.05) and 3 (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Exercise and blood lymphocyte subset responses: intensity, duration, and subject fitness effects.

This study examined the effect of exercise intensity and duration on the percent blood lymphocytes in men of low [LF; maximal O2 uptake (VO2max) less than 50 ml.kg-1.min-1 and sedentary], moderate (MF; VO2max = 50-60 ml.kg-1.min-1 and recreationally active), and high (HF; VO2max greater than 60 ml.kg-1.min-1 and recent training history) fitness. Thirty healthy adult men (aged 20-31 yr) participated in four randomly ordered cycle ergometer rides: ride 1 (65% VO2max, 30 min), ride 2 (30% VO2max, 60 min), ride 3 (75% VO2max, 60 min), and ride 4 (65% VO2max, 120 min). Blood samples were drawn at various times before and after the exercise sessions. Lymphocyte subsets were determined by flow cytometry using monoclonal antibodies for total T (CD3+), T-helper (CD4+), and T-suppressor (CD8+) lymphocytes and for a subset of cells expressing a natural killer (NK) cell antigen (Leu7+). Plasma catecholamines were assayed to determine exercise stress. There were sharp reductions (P less than 0.01) in the percentage of pan-T and T-helper lymphocytes immediately after exercise across all fitness levels; the magnitude of this reduction was greatest after the highest intensity (ride 3) or longest duration (ride 4) work. In contrast, the absolute number of T and T-helper cells tended to increase after exercise and significantly so in the HF subjects (P less than 0.005). There was no significant effect of exercise or subject fitness category on the percentage of T-suppressor lymphocytes, although the absolute numbers of this subset increased significantly after exercise in LF subjects. Marked increases (P less than 0.01) in the percentage of NK cells occurred immediately after exercise at all intensities and durations tested; numerical increases in total NK cells were significant in all fitness groups after the highest intensity work (ride 3; P less than 0.005). Irrespective of whether the changes were expressed as percentage or total numbers, recovery to base line occurred at 30 min after exercise. The results suggest that the exercise effect on blood lymphocyte subset percentages in men is transient and occurs across all fitness levels. Concomitant changes in plasma catecholamine concentrations are only weakly associated with these lymphocyte subset percentage responses to exercise. Furthermore, this study shows that the exercise-induced changes in lymphocyte percentages do not consistently reflect changes in the absolute numbers of cells.

Adult↗

Exercise stress and murine natural killer cell function.

Male C3He mice were trained to run on a treadmill (final speed, slope, and duration of 30 m/min, 8 degrees, 30 min/day, 5 days/week, respectively) for 10 weeks or they remained sedentary. At the end of the training program, half of the mice were sacrificed and half were given a single bout of exercise to exhaustion (50% stepwise increases in final running speed for 2-min intervals). Splenic catecholamine concentrations, splenic natural killer cell cytolytic activity against YAC-1 tumor targets, and frequency of asialo GM1 (a murine natural killer cell surface glycolipid)-positive splenocytes were assessed. Exhaustive exercise in both trained and untrained mice reduced the in vitro killing of tumor targets by splenic natural killer cells relative to killing by splenocytes from mice which did not undergo the acute exercise bout (P less than 0.05). The frequency of asialo GM1-positive splenocytes was also reduced in the exhaustively exercised animals (P less than 0.05). Training alone, without the additional stress of exhaustive exercise, reduced the frequency of asialo GM1-positive splenocytes relative to a sedentary condition (P less than 0.05), but did not compromise natural killer cell cytolytic activity against the tumor targets. Splenic epinephrine concentrations in the exhaustively exercised animals were elevated 3- to 5-fold above the concentrations observed in trained and sedentary mice. These results suggest that a single, acute exercise bout reduces the capacity of splenic natural killer cells to kill tumor targets in vitro and that training enhances splenic natural killer cell cytolytic activity, on a per cell basis, against tumor targets.

Animals↗

Exercise stress alters the percentage of splenic lymphocyte subsets in response to mitogen but not in response to interleukin-1.

Results of previous work from this laboratory demonstrated that reduced murine splenic lymphocyte proliferation in response to Concanavalin A (Con A) is associated with acute exercise stress. The present study was conducted to determine whether the stress of physical work further affects the expression of splenic lymphocyte phenotypes following in vitro stimulation by the T-cell mitogen, Con A, and also by interleukin-1 (IL1). Mice in this study were assigned to one of five treatment conditions. Two groups of mice were exposed only to the noise and vibration of a treadmill for 8 weeks; one of these groups was given an acute exhaustive run. Three groups of mice were exposed to 8 weeks of treadmill training: one group was sacrificed immediately after training, a second group was sacrificed 72 h after training, and a third group was rested for 72 h and then given an acute exhaustive run. There was a significant effect of stimulation by Con A on the percentage of splenic lymphocytes positive for Thy1.2, Lyt-2, L3T4, and goat anti-mouse Ig, regardless of treatment condition. Acute exercise, however, affected the magnitude of the response. There was a significantly greater increase in the percentage of Thy1.2+ and, especially of, Lyt-2+ cells in stimulated splenic lymphocytes from untrained mice given an exhaustive exercise session compared with controls and with trained mice. There was no significant effect of the addition of IL1 to any culture, irrespective of treatment condition. These results suggest that reduced mitogenesis after acute exercise stress exposure may be related to the increased appearance of Lyt-2+ (T suppressor) cells.

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