Peripheral inflammatory cytokines and motor symptoms in persons with Parkinson's disease.

Background: Many of the motor symptoms of Parkinson's disease (PD) impact quality of life and are not fully ameliorated by current pharmacological and surgical treatments. A better understanding of the pathophysiology underlying these symptoms is needed. Previous research has suggested that inflammation may play a significant role in PD pathophysiology and progression, but there is limited research exploring how inflammation directly relates to motor symptoms in PD. Thus, the purpose of this study was to evaluate associations between peripheral immune inflammatory markers and motor symptoms of PD, specifically, tremor, bradykinesia, and postural and gait instability. We hypothesized that peripheral inflammatory cytokines would predict the severity of motor symptoms in persons with PD, and that there will be higher levels of peripheral inflammatory cytokine markers in persons with PD when compared to age-matched healthy older adults. Methods: Twenty-six participants with PD and fourteen healthy older adults completed the study. For participants with PD, the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) was recorded and scored by two Movement Disorders Neurologists masked to the study. A blood sample was collected from both participants with PD and the healthy older adults. Through the MILLIPLEX® map High Sensitivity Human Cytokine Kit, key inflammation-related markers were analyzed (TNF-α, IFN-γ, IL-1ß, IL-8, IL-2, IL-7, IL-5, IL-13, IL, 4, IL-10 IL-12p70, GM-CSF, and IL-6). Results: Results revealed significantly higher levels of IL-6 in persons with PD when compared to healthy older adults (p â€‹= â€‹0.005). Moreover, results revealed that higher levels of IL-4 (p â€‹= â€‹0.011) and lower levels of IFNγ (p â€‹= â€‹0.003) significantly predicted more severe tremor in persons with PD. No other associations between the peripheral inflammation markers and other motor symptoms were observed. Conclusions: Overall, these results are consistent with a growing body of literature that implicates inflammatory cytokines in the PD, and further suggests that inflammatory cytokines, or lack thereof, may be associated with tremor in persons with PD.

Contribution of serum inflammatory markers to changes in bone mineral content and density in postmenopausal women: a 1-year investigation.

Bone formation and resorption are influenced by inflammatory processes. We examined the relationships among inflammatory markers and bone mineral content (BMC) and density (BMD) and determined the contribution of inflammatory markers to 1-yr changes in BMC and BMD in healthy postmenopausal women. This analysis included 242 women at baseline from our parent Soy Isoflavones for Reducing Bone Loss project who were randomly assigned to 1 of 3 treatment groups: placebo, 80 mg/d soy isoflavones, or 120 mg/d soy isoflavones. BMD and BMC from the lumbar spine (LS), total proximal femur (hip), and whole body were measured by dual energy X-ray absorptiometry and the 4% distal tibia by peripheral quantitative computed tomography. Serum inflammatory markers (C-reactive protein, interleukin [IL]-1 beta, IL-6, tumor necrosis factor-alpha [TNF-alpha], and white blood cell count [WBC]) were measured at baseline, 6, and 12 mo. Because of attrition or missing values, data analysis at 12 mo includes only 235 women. Significant associations among IL-6, TNF-alpha, and WBC were observed with percent change in LS, hip, and whole body BMC and BMD. Multiple regression analysis indicated that in combination inflammatory markers accounted for 1.1-6.1% of the variance to the observed 12-mo changes in BMC and BMD. Our results suggest that modifying inflammatory markers, even in healthy postmenopausal women, may possibly reduce bone loss.

Aerobic exercise, but not flexibility/resistance exercise, reduces serum IL-18, CRP, and IL-6 independent of beta-blockers, BMI, and psychosocial factors in older adults.

Increased serum levels of inflammatory mediators have been associated with numerous disease states including atherosclerosis, Type II diabetes, hypertension, depression, and overall mortality. We hypothesized that a long-term exercise intervention among older adults would reduce serum inflammatory cytokines, and this reduction would be mediated, in part, by improvements in psychosocial factors and/or by beta-adrenergic receptor mechanisms. Adults age 64 were randomly assigned to either an aerobic exercise treatment (CARDIO) or a flexibility/strength exercise treatment (FLEX) 3 days/week, 45 min/day for 10 months. A subgroup of subjects treated with non-selective beta(1)beta(2) adrenergic antagonists were included to evaluate the potential role of beta-adrenergic receptor adaptations as mediators of an exercise-induced change in inflammation. The inflammatory mediators [C-reactive protein (CRP), IL-6, tumor necrosis factor (TNF)-alpha, and IL-18] and the psychosocial factors (depression, perceived stress, optimism, sense of coherence, and social support) were measured pre- and post-intervention. The CARDIO treatment resulted in significant reductions in serum CRP, IL-6, and IL-18 compared to the FLEX treatment (significant treatment x time interaction, p<.05), whereas TNFalpha declined in both groups (main effect of time, p=.001). However, several psychosocial factors (depression, optimism, and sense of coherence) improved in both groups suggesting that the reduction of CRP, IL-6, and IL-18 in the CARDIO group was not mediated by improvements in psychosocial scores. With respect to the potential role of beta-adrenergic receptors, both CARDIO subjects treated with beta-adrenergic antagonists and those who were not treated with those medications demonstrated similar reductions in serum CRP, IL-6, IL-18, and TNFalpha. In summary, we have observed that an aerobic exercise intervention can significantly reduce serum inflammatory mediators, but beta-adrenergic receptors and psychosocial factors do not appear to be involved.

Low-level dietary deoxynivalenol and acute exercise stress result in immunotoxicity in BALB/c mice.

We hypothesized that acute exercise stress would exacerbate immunosuppressive effects of sub-acute exposure to dietary deoxynivalenol (DON). Male BALB/c mice were fed 0 or 2 mg DON/kg diet for 14 days, 12 animals per dose, and then exercised to fatigue on a treadmill. Mice were euthanized by decapitation, trunk blood and spleens were collected. Single-cell suspensions of splenocytes were used to quantify immune function by plaque hemolysis and conconavalin-A (ConA) stimulated lymphocyte proliferation assays. Serum corticosterone level was determined by enzyme immunoassay. Only the nonexercised DON-fed mice showed significant splenocyte proliferation suppression, 32.9 +/- 17.9% of nonexercised controls (p = 0.021). Exercised controls and DON-fed exercised animals showed splenocyte proliferation of 68-75% of nonexercised controls. Antibody response to a T-dependent antigen, sheep red blood cells, was significantly less for exercised DON-fed mice than in controls (p = 0.031). Serum corticosterone levels were significantly higher for both exercised groups compared to the unexercised groups (p < 0.001). IL-4 secretion from mitogen-stimulated splenocytes was elevated by DON alone (p < 0.05) while IL-2 was elevated by DON with exercise stress (p < 0.05). Our hypothesis was confirmed with respect to T-lymphocyte-dependent antibody production, but not for splenocyte proliferation. Exercise stress abrogated DON-mediated suppression of splenocyte proliferation, perhaps mediated by induction of elevated stress hormones counteracting cytokine expression alterations of DON.

The exercise-induced enhancement of influenza immunity is mediated in part by improvements in psychosocial factors in older adults.

The primary goal of this study was to determine whether exercise-associated improvements of the immune response to influenza vaccination were mediated by improvements in psychosocial factors in older adults. At baseline, prior to the exercise intervention, older adult participants were immunized with influenza vaccine. Blood samples collected pre-immunization, 1, 4, and 12 weeks post-immunization were analyzed for anti-influenza antibody, whereas influenza-specific cytokine (IFNgamma) was evaluated at 1 week post-immunization. Depression and sense of coherence were measured pre-immunization. Four weeks post-immunization, participants were randomly assigned to either an aerobic exercise group (n=14) or a control group (n=14). After a 10-month exercise intervention, the immunization, blood collections, and psychosocial measures were repeated. At the post-intervention evaluation, exercise participants had improved scores on depression and sense of coherence. Also post-intervention, exercise participants had a greater increase in antibody and IFNgamma production. After controlling for the effect of both psychosocial measures, the exercise treatment remained significant with respect to antibody titer suggesting that the increases in antibody were not mediated by improvement in the psychosocial factors. In contrast, the enhancement of IFNgamma appeared to be mediated at least in part by the psychosocial factors. After controlling for psychosocial factors, exercise treatment was no longer significantly related to the change in IFNgamma. Taken together, our findings may suggest that the mechanism(s) of exercise-induced improvement in immunocompetence involve both physiological and psychological pathways.

Glucocorticoids produced during exercise may be necessary for optimal virus-induced IL-2 and cell proliferation whereas both catecholamines and glucocorticoids may be required for adequate immune defense to viral infection.

Prolonged, exhaustive exercise has been associated with impaired immune responsiveness and increased susceptibility to infection. We have shown that one bout of exercise to fatigue followed by viral challenge increases mortality. Stress hormones such as corticosteroids and catecholamines have been suggested as potential mediators of exhaustive exercise-induced immunosuppression. The purpose of this study was to determine whether the administration of pharmacological agents to block the effect of catecholamines or corticosteroids would minimize the immunosuppression associated with this type of exercise. Mice either exercised to fatigue or were exposed to control conditions, and mice received an i.p. injection of either nadolol (beta-adrenergic receptor antagonist), RU486 (glucocorticoid type II receptor antagonist), or vehicle. Fifteen minutes post-exercise, mice were exposed to viral infection (Herpes simplex virus; HSV) via an intranasal route, and cells were collected 3 days post-infection. The results showed that exercise suppressed HSV-specific cell proliferation, HSV-specific IL-2, and IFN-gamma, but did not alter these same immune parameters when the mitogen ConA was used to stimulate cells. In addition, exercise reduced NK cell cytotoxicity, alveolar cell TNFalpha, and peritoneal IL-1beta, but did not affect IL-10. The pharmacological blockade did not attenuate the exercise-associated immunosuppression. In fact, RU486 treatment exacerbated the exercise-induced decline in HSV-induced IL-2 production and cell proliferation. RU486 and nadolol treatment also tended to decrease IL-10, IFN-gamma, TNFalpha (nadolol only), and IL-1beta (RU486 only) in both exercise and control mice, suggesting that stress hormones may be necessary during infection for optimal responsiveness. These findings suggest that suppression of immune defenses during viral infection persists for at least 3 days post-exercise, and stress hormones may be essential for optimal immune defense to viral challenge, rather than detrimental.

Effects of androstenedione-herbal supplementation on serum sex hormone concentrations in 30- to 59-year-old men.

The effectiveness of a nutritional supplement designed to enhance serum testosterone concentrations and prevent the formation of dihydrotestosterone and estrogens from the ingested androgens was investigated in healthy 30- to 59-year old men. Subjects were randomly assigned to consume DION (300 mg androstenedione, 150 mg dehydroepiandrosterone, 540 mg saw palmetto, 300 mg indole-3-carbinol, 625 mg chrysin, and 750 mg Tribulus terrestris per day; n = 28) or placebo (n = 27) for 28 days. Serum free testosterone, total testosterone, androstenedione, dihydrotestosterone, estradiol, prostate-specific antigen (PSA), and lipid concentrations were measured before and throughout the 4-week supplementation period. Serum concentrations of total testosterone and PSA were unchanged by supplementation. DION increased (p < 0.05) serum androstenedione (342%), free testosterone (38%), dihydrotestosterone (71%), and estradiol (103%) concentrations. Serum HDL-C concentrations were reduced by 5.0 mg/dL in DION (p < 0.05). Increases in serum free testosterone (r2 = 0.01), androstenedione (r2 = 0.01), dihydrotestosterone (r2 = 0.03), or estradiol (r2 = 0.07) concentrations in DION were not related to age. While the ingestion of androstenedione combined with herbal products increased serum free testosterone concentrations in older men, these herbal products did not prevent the conversion of ingested androstenedione to estradiol and dihydrotestosterone.

Endocrine and lipid responses to chronic androstenediol-herbal supplementation in 30 to 58 year old men.

OBJECTIVE: The effectiveness of an androgenic nutritional supplement designed to enhance serum testosterone concentrations and prevent the formation of dihydrotestosterone and estrogen was investigated in healthy 3 to 58 year old men. DESIGN: Subjects were randomly assigned to consume a nutritional supplement (AND-HB) containing 300-mg androstenediol, 480-mg saw palmetto, 450-mg indole-3-carbinol, 300-mg chrysin, 1,500 mg gamma-linolenic acid and 1.350-mg Tribulus terrestris per day (n = 28), or placebo (n = 27) for 28 days. Subjects were stratified into age groups to represent the fourth (30 year olds, n = 20), fifth (40 year olds, n = 20) and sixth (50 year olds, n = 16) decades of life. MEASUREMENTS: Serum free testosterone, total testosterone, androstenedione, dihydrotestosterone, estradiol, prostate specific antigen and lipid concentrations were measured before supplementation and weekly for four weeks. RESULTS: Basal serum total testosterone, estradiol, and prostate specific antigen (PSA) concentrations were not different between age groups. Basal serum free testosterone concentrations were higher (p < 0.05) in the 30- (70.5 +/- 3.6 pmol/L) than in the 50 year olds (50.8 +/- 4.5 pmol/L). Basal serum androstenedione and dihydrotestosterone (DHT) concentrations were significantly higher in the 30- (for androstenedione and DHT, respectively, 10.4 +/- 0.6 nmol/L and 2198.2 +/- 166.5 pmol/L) than in the 40- (6.8 +/- 0.5 nmol/L and 1736.8 +/- 152.0 pmol/L) or 50 year olds (6.0 +/- 0.7 nmol/L and 1983.7 +/- 147.8 pmol/L). Basal serum hormone concentrations did not differ between the treatment groups. Serum concentrations of total testosterone and PSA were unchanged by supplementation. Ingestion of AND-HB resulted in increased (p < 0.05) serum androstenedione (174%), free testosterone (37%), DHT (57%) and estradiol (86%) throughout the four weeks. There was no relationship between the increases in serum free testosterone, androstenedione, DHT, or estradiol and age (r2 = 0.08, 0.03, 0.05 and 0.02, respectively). Serum HDL-C concentrations were reduced (p < 0.05) by 0.14 mmol/L in AND-HB. CONCLUSIONS: These data indicate that ingestion of androstenediol combined with herbal products does not prevent the formation of estradiol and dihydrotestosterone.

Moderate exercise is associated with enhanced antigen-specific cytokine, but not IgM antibody production in aged mice.

It has been suggested that moderate exercise may modulate the immune response in the elderly. We investigated whether moderate exercise had an effect on the immune response to viral infection in both young (2-4 months) and older (16-18 months) male BALB/cJ mice. Exercised (EX) mice ran on a treadmill for 8 weeks at a gradually increasing speed and duration whereas control (CON) mice were only handled briefly during each exercise session and then returned to their cages. Mice were infected with herpes simplex virus type 1 (HSV-1) 24 h post-exercise. Serum IgM anti-HSV antibody, HSV-1 specific Th1/Th2 cytokine production by spleen cells, and cytokine production by alveolar cells were measured 7 days post-infection. In the aged mice, exercise was associated with an enhanced production of the HSV-1 specific Th1-associated cytokines, interleukin (IL)-2 and interferon (IFN)-gamma, but had no effect on the Th2-associated cytokine IL-10 or IgM antibody. No effect of exercise was observed in young mice. IL-12 production was not altered by exercise, but aging was associated with altered IL-12 production in a tissue-specific manner. In conclusion, moderate exercise was associated with increased antigen-specific IL-2 and IFN-gamma production in response to viral challenge in older mice.

Prolonged exercise suppresses antigen-specific cytokine response to upper respiratory infection.

Fatiguing exercise has been associated with an increased susceptibility to infection. This study examined the antigen-specific T-helper (Th) type 1 and Th type 2 cytokine response to herpes simplex virus (HSV) infection after an acute bout of fatiguing exercise. Male BALB/cJ mice ran on a treadmill (Ex) until voluntary fatigue (approximately 2.5 h), and control mice were handled and remained next to the treadmill. Mice were infected with HSV 20 min after exercise. Mice were killed 2 or 7 days postinfection, and sera and spleens were taken for the determination of HSV-specific serum IgM, splenocyte cytokine production during culture with HSV, and splenocyte natural killer cell cytotoxicity. Both Th type 1 [interleukin (IL)-2, interferon-gamma, IL-12] and Th type 2 (IL-10) cytokine production in spleen cell cultures, as well as natural killer cell cytotoxicity, decreased in Ex on day 2 postinfection. On day 7 postinfection, there was no difference in HSV-specific serum IgM or cytokine production by cells from control and Ex mice, with the exception of decreased IL-12 in Ex mice. These findings suggest that fatiguing exercise may alter the kinetics of antigen-specific cytokine production.

Endocrine responses to chronic androstenedione intake in 30- to 56-year-old men.

In young men, chronic ingestion of 100 mg androstenedione (ASD), three times per day, does not increase serum total testosterone but does increase serum estrogen and ASD concentrations. We investigated the effects of ASD ingestion in healthy 30- to 56-yr-old men. In a double-blind, randomly assigned manner, subjects consumed 100 mg ASD three times daily (n = 28), or placebo (n = 27) for 28 days. Serum ASD, dihydrotestosterone (DHT), free and total testosterone, estradiol, prostate-specific antigen (PSA), and lipid concentrations were measured at week 0 and each week throughout the supplementation period. Serum total testosterone and PSA concentrations did not change with supplementation. Elevated serum concentrations of ASD (300%), free testosterone (45%), DHT (83%), and estradiol (68%) were observed during weeks 1-4 in ASD (P < 0.05). There was no relationship between age and changes in serum ASD (r2 = 0.024), free testosterone (r2 = 0.00), or estradiol (r2 = 0.029) concentrations with ASD, whereas the serum DHT response to ASD ingestion was related to age (r2 = 0.244; P < 0.05). Serum concentrations of high-density lipoprotein cholesterol were decreased by 10% during the supplementation period (P < 0.05). These results suggest that the ingestion of 100 mg ASD, three times per day, does not increase serum total testosterone or PSA concentrations but does elicit increases in ASD, free testosterone, estradiol, and DHT and decreases serum high-density lipoprotein cholesterol concentrations.

Exercise effects on IFN-beta expression and viral replication in lung macrophages after HSV-1 infection.

Mice exercised to fatigue and exposed to herpes simplex virus type 1 (HSV-1) exhibit greater mortality than control mice. In this study, we examined lung macrophage resistance to HSV-1 after exercise in terms of both viral replication and interferon (IFN)-beta production. We utilized the reverse transcriptase-rapid polymerase chain reaction to measure the IFN-beta mRNA content in alveolar macrophages. IFN release was measured with a bioassay, and viral replication within the macrophage was assessed by plaque titration. Exercised (Ex) mice ran on a treadmill until fatigue while control (Con) mice remained in lanes above the treadmill. After exercise, alveolar macrophages were removed and incubated with HSV-1. Alveolar macrophage IFN-beta mRNA was greater in Ex than in Con mice. Culture supernatant from infected macrophages showed a higher degree of IFN release and a higher number of infectious viral particles in Ex vs. Con mice. It is likely that the increase in IFN-beta mRNA occurs in response to a higher degree of viral replication. These results suggest that macrophages from Ex mice are less resistant to infection with HSV-1.

Exercise effects on lung tumor metastases and in vitro alveolar macrophage antitumor cytotoxicity.

This study examined the effects of moderate and prolonged exercise on 1) lung tumor metastases and 2) alveolar macrophage antitumor response in vitro. C57B1/6 mice were assigned to either Ex-30 (30-min run), Ex-F (run to fatigue), Ex-F-24 h (run to fatigue 24 h before tumor injection), or Con (rested in lanes above the treadmill). Mice received intravenous injections of syngeneic B16 melanoma cells 30 min postexercise. Lungs were removed 7 or 10 days later, and tumor foci were counted. Ex-F had fewer tumors than either Ex-30 or Con, whereas Ex-F-24 h also showed a strong trend toward fewer tumors. The initial localization of tumor cells in the lungs after injection was not different among groups. For the in vitro experiment, mice were killed immediately after exercise or 8 h later. Alveolar macrophages were removed and cultured in vitro with B16 melanoma cells. The growth of the tumors cultured with macrophages from Ex-F was lower than Con after exercise and, to a lesser extent, 8 h later. In Ex-30, this effect was only found immediately after exercise. The data suggest that prolonged exercise has a protective effect on lung tumor metastases and enhances alveolar macrophage antitumor cytotoxicity.

Immune system activation and fatigue during treadmill running: role of interferon.

UNLABELLED: Extreme fatigue often accompanies infection and other diseases, but the causal mechanisms are unknown. Recent research has focused on various cytokines as potential immune system mediators of fatigue during illness. Interferon-alpha/beta (IFN-alpha/beta) has attracted the most interest in this regard. PURPOSE: The purpose of this research was to study the effect of IFN-alpha/beta on fatigue during treadmill running in mice. METHODS: Mice (male CD-1) were acclimated to treadmill running for 4 d before experimental sessions. In experiment 1 (EXP 1), mice were injected with either polyI:C (pI:C) (5 mg.kg-1 body weight) or saline (CON) 12 or 24 h before the exercise session. These sessions consisted of treadmill running to fatigue (approximately 3 h, 19-24 m.min-1, 5% grade, no shock). In experiment 2 (EXP 2), mice were injected 24 h before exercise with normal rabbit serum (CON), pI:C, or pI:C + anti-IFN-alpha/beta antibody (pI:C + Ab). RESULTS: The results of EXP 1 showed that the plasma IFN-alpha/beta titer was much higher at 24 h than at 12 h after pI:C injection (P < 0.001) and that run time to fatigue was significantly reduced only when the exercise occurred 24 h after injection (P < 0.05). In EXP 2, administration of the anti-IFN-alpha/beta antibody attenuated both the pI:C-induced increase in plasma IFN-alpha/beta (P < 0.001) and the decrease in run time to fatigue (r = -0.81, P < 0.001). CONCLUSIONS: These results suggest that immune system activation by pI:C was associated with early fatigue during prolonged treadmill exercise and that this effect may, at least partially, result from increased IFN-alpha/beta.

The role of stress hormones in exercise-induced suppression of alveolar macrophage antiviral function.

We hypothesized that a previously observed exercise-induced suppression of alveolar macrophage antiviral resistance results from increases in corticosterone and/or epinephrine. Mice (CD-1) were run to fatigue on a treadmill (exercise), or placed in Plexiglas lanes above the treadmill (control). The role of corticosterone was assessed by further dividing mice into groups receiving one of the following treatments; sham surgery, adrenalectomy, or adrenalectomy plus corticosterone replacement. Macrophage antiviral function was suppressed in the exercised mice compared to the control mice. However, macrophage antiviral function was not suppressed in the exercised mice that underwent adrenalectomy or adrenalectomy plus corticosterone replacement. We tested whether another adrenal factor (epinephrine) may be involved by dividing mice into exercise and control groups treated with either saline or propranolol. Macrophage antiviral function was again suppressed in the saline-treated exercised mice compared to saline-treated control mice, but no differences were found between the exercised mice receiving propranolol, control mice receiving propranolol, or saline-treated control mice. Isoproterenol, when added to alveolar macrophages in culture, also suppressed antiviral resistance. These findings suggest that decreased macrophage antiviral function following exercise may be due to increased release of adrenal catecholamines.

Effects of exercise intensity on natural killer cell activity in women.

Exercise effects on natural killer cell (NK) activity in men appear to be intensity dependent, but there is very little data in women. We tested the effect of high versus moderate-intensity exercise relative to non-exercising controls on NK cytolytic activity (NK activity) in women using oral contraceptives. Subjects (n = 8) participated in 3 treatments consisting of 25 min of cycle ergometer exercise at 80% (HI-INT) and 40% (MOD-INT) VO2max, and a 25 min control (CON) session in which the subject remained seated on the cycle ergometer, but did not exercise. Blood was obtained prior to exercise, immediately after, and at 90 min and 3 h after exercise. During CON, NK activity gradually increased and cortisol gradually decreased during the approximately 3.5 h experimental period. Relative to CON, HI-INT increased NK activity, %CD56+ (NK) cells, and plasma norepinephrine immediately post exercise (p < or = 0.05). There was also a trend for decreased NK activity at 90 min (p = 0.075). No differences among treatment groups were found by 3 h post exercise. In MOD-INT, there were no differences from CON in any variable at any time. These data suggest that the typical NK response to intensive exercise in men, which consists of a brief increase followed by a more prolonged suppression, also occurs in women using oral contraceptives. However, it is important to use time-matched control measurements in determining this response.

Exercise, alveolar macrophage function, and susceptibility to respiratory infection.

The effects of exercise on susceptibility to respiratory infection were determined by using a murine model of intranasal challenge with herpes simplex type 1 virus (HSV-1). Two doses of treadmill exercise were assessed: moderate short-term (30 min) exercise and prolonged strenuous exercise to voluntary fatigue (2.5-3.5 h). Morbidity and mortality among exercised and control mice were compared after intranasal challenge with HSV-1. We also assessed the ability of alveolar macrophages to restrict HSV-1 viral replication (intrinsic resistance) among exercise and control groups of mice at several time points postexercise. Exercise to fatigue followed by exposure to viral infection resulted in greater morbidity and mortality than either no exercise or short-term moderate exercise. In addition, antiviral resistance of macrophages obtained from the lungs of both exercised groups was suppressed, albeit for a longer duration in the fatigued group. These data are particularly important in that they identify an exercise-induced decrease in antiviral resistance of a specific component of the immune system within the lungs, in conjunction with increased susceptibility to respiratory infection in vivo. The specific mechanism of decreased antiviral resistance of alveolar macrophages and its role in respiratory infection after exercise remains to be determined.

Effects of exercise on the immune response to cancer.

This study examined the effects of two doses of exercise on tumor incidence and progression, and the number and activity of intratumoral phagocytic cells (80% macrophages [M phi's]). Male mice were randomly assigned to control (CON), moderate (MOD) or exhaustive (EXH) treadmill running. Mice were inoculated subcutaneously with 2.5 x 10(5) mammary adenocarcinoma cells after 3 d of running (3 h after the last run at a point when enhancement in M phi cytotoxicity is observed). This tumor was chosen due to its susceptibility to M phi inhibition in vitro and in vivo. Mice continued daily running for 14 d. Food intakes were higher during the last 3 d in MOD and EXH, but body weights were no different. Flow cytometer analysis of tumor masses revealed that MOD had greater numbers of phagocytic cells (vs EXH) with slightly higher phagocytic activities (vs CON and EXH) (P < 0.05). However, no group differences in tumor appearance were seen except on day 7 when CON had less observable tumors than MOD and EXH (P < 0.05). Tumor size was also not different between groups at any point. These results indicate that moderate exercise can increase the phagocytic capacity of intratumoral phagocytic cells, but these changes had no apparent effect on tumor incidence or progression in this study.