Biomedical subjects

Brian K McFarlin

Publications and source records attributed to Brian K McFarlin.

12 recordsLinked to original sources

PubMed2006

Carbohydrate consumption during cycling increases in vitro NK cell responses to IL-2 and IFN-gamma.

INTRODUCTION: Exercise has been shown to lower blood natural killer cell concentration and activity for up to 24-h after exercise; however, the mechanism underlying this effect is not clearly defined. We have speculated that an exercise-induced change in T-cell control of NK cells is at least partly responsible for the post-exercise suppression. As a follow-up to our previous research, the purpose of this study was to examine the T and NK cells responses during and following moderate/high-intensity endurance exercise. METHODS: Eight male subjects (20+/-1 y; VO(2peak)=67.22+/-2.79 mL.kg(-1).mL(-1)) were recruited to complete two 1-h (75-80% VO(2peak)) cycling trials in a random counterbalanced order: carbohydrate (CHO) and placebo (PLA). Venous blood samples were collected before (PRE), immediately (POST), 2-h (2H), and 4-h (4H) after exercise. NK (CD3(-)/56(+)) and activated NK (CD3(-)/56(+)/69(+)) number were measured using flow cytometry. NK cell activity (NKCA) was determined using both a (51)Cr release assay (NKCA-51) and activated NK cell number (NKCA-69). Whole blood samples were stimulated with IL-2, IFN-gamma, IL-4, IL-12, and no stimulation for 12-h and then analyzed for NK cell activity using a (51)Cr release assay (NKCA-51). RESULTS: Leukocyte counts and unstimulated NKCA were not different between CHO and PLA; however, exercise significantly increased NKCA (P<.05). Fold change in IL-2, IFN-gamma, and IL-2+IFN-gamma-stimulated NKCA were significantly greater in CHO compared to PLA (P<.05). No effect of drink was found for IL-4, IL-12, and IL-4+IL-12-stimulated NKCA. DISCUSSION: The fold change in IL-2-stimulated NKCA is consistant with our previous published work. The drink effect for Th1 (but not Th2) cytokines suggests they may play a more significant role in modulating NKCA following a strenuous bout of aerobic exercise when CHO is consumed.

Adult↗

PubMed2006

Energy restriction with different protein quantities and source: implications for innate immunity.

OBJECTIVE: Physical age, energy restriction (ER), and weight loss have been reported to suppress indices of innate immunity, which may increase the risk of illness. To evaluate these interactions, we recruited older, postmenopausal women (50 to 80 years) to fill one of the following 9-week ER (1250 kcal/d) groups: beef [n = 14; reported intakes 46% carbohydrate (CHO):24% protein (PRO):30% fat], chicken (n = 15; 51% CHO:25% PRO:24% fat), or CHO (n = 14; 59% CHO:17% PRO:24% fat), or a non-intervention control (n = 11). RESEARCH METHODS AND PROCEDURES: Fasting blood was collected before and after ER to determine leukocyte phenotype, neutrophil oxidative burst capacity, natural killer cell activity, stimulated interleukin-2 and interferon-gamma production, and blood zinc and iron concentrations. RESULTS: No significant effects of ER (8.6% weight loss) or PRO quantity and source were found for the majority of indices of innate immunity. Small but significant (p < 0.05) declines in interleukin-2 production were found in the chicken and CHO groups only; however, the clinical significance of this finding is not known. DISCUSSION: In the present study, 9 weeks of moderate ER did not suppress immunity in postmenopausal women. Also, contrary to our hypothesis, differential zinc and iron intakes did not significantly alter immunity.

Aged↗

PubMed2006

Physical activity status, but not age, influences inflammatory biomarkers and toll-like receptor 4.

BACKGROUND: Chronic inflammation has been implicated in the development of cardiovascular disease, diabetes mellitus, cachexia, and osteoporosis. Regular physical activity has been purported to possess "anti-inflammatory" properties which may limit chronic inflammation. Recently, we hypothesized that toll-like receptor 4 (TLR4) may play a role in activity-induced modulation of inflammation. Therefore, the purpose of this study was to determine the association between age, physical activity status, biomarkers of inflammation, and TLR4. METHODS: Male and female participants (n = 84) were recruited to fill one of the following groups: young (18-30 years), active; young, inactive; old (60-80 years), active; or old, inactive. To assess physical activity status, participants completed a Paffenbarger Physical Activity Questionnaire and a modified Balke submaximal treadmill test. After grouping and screening, participants were given a standard mixed diet to consume 24 hours prior to arriving at the laboratory. Participants were instructed to consume all food by 10 pm the night prior to blood sampling (8-hour fast). Following 30 minutes of seated rest in a quiet room, venous blood samples were collected. Lipopolysaccharide-stimulated inflammatory cytokine production and plasma high-sensitivity C-reactive protein (hsCRP) were determined by enzyme-linked immunosorbent assay, and TLR4 expression was determined by flow cytometry. RESULTS: Lipopolysaccharide-stimulated interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha production, TLR4 expression, and hsCRP were significantly lower in active compared to inactive participants (p <.05). Also, older participants had significantly higher hsCRP than young participants had (p <.05). CONCLUSIONS: The findings of the present study support previous reports which infer that acute exercise or a physically active lifestyle may possess anti-inflammatory properties. Also this study, along with previous work from our laboratory, suggests that TLR4 may play a role in regulating the link between inflammatory cytokine production and a physically active lifestyle.

Adult↗

PubMed2006

Toll-like receptor 4: link to the anti-inflammatory effects of exercise?

Evidence is emerging that exercise training has anti-inflammatory effects. Our early finding that blood cultures from trained subject had a reduced responsiveness to lipopolysaccharide led to a series of studies in which we measured toll-like receptor 4--the primary signaling receptor for lipopolysaccharide. The toll-like receptor 4 expression was consistently lower in physically active subjects compared with inactive subjects and reduced after training in previously inactive subjects.

Cytokines↗

PubMed2005

Influence of exercise training and age on CD14+ cell-surface expression of toll-like receptor 2 and 4.

The influence of an exercise training program and age on inflammatory cytokine production and CD14+cell-surface expression of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) was examined in 60 younger and older subjects. Subjects were assigned to: young physically active (YPA, n = 15; 25.2 +/- 5.0 years), young physically inactive (YPI, n = 14; 24.9 +/- 4.7 years), older physically active (OPA, n = 14; 71.2 +/- 4.4 years) or older physically inactive (OPI, n = 17; 71.0 +/- 4.3 years) groups. YPI and OPI completed 12 weeks (3 days/week) of endurance (20 min) and resistance exercise (eight exercises, two sets). YPA and OPA groups were instructed to continue their normal activity for 12 weeks. Blood was collected at rest, before and after the 12-week training and control period. A whole blood method was used to determine lipopolysaccharide-(LPS) and peptidoglycan-(PGN) stimulated IL-6, IL-1beta, and TNF-alpha production with supernatants analyzed using ELISA. CD14+ cell-surface expression of TLR2 and TLR4 were measured using flow cytometry. Training increased estimated VO(2max) by 10.4% and increased strength by an average of 38.1%. YPI and OPI had a post-training reduction in LPS-stimulated IL-6 production (P < .01), but LPS-stimulated IL-1beta and TNF-alpha and PGN-stimulated cytokines were not changed. CD14+ cell TLR4 was significantly reduced (P < .05) in YPI and OPI groups after training, but TLR2 was not significantly changed. An exercise training program reduced LPS-stimulated IL-6, concomitant with lower TLR4. These results provide further support for a training- or physical activity-induced lowering of TLR4 and inflammation.

Adolescent↗

PubMed2005

Chronic resistance exercise training improves natural killer cell activity in older women.

BACKGROUND: Regular exercise has been reported to slow the age-associated declines in natural killer cell activity (NKCA). To evaluate this response, we recruited older, postmenopausal women (65-85 years old) to fill one of two groups: training (10 weeks of resistance exercise; TR) or control. METHODS: Blood samples were collected from an arm vein in the TR group at rest (PRE), immediately following (POST), and 2 hours (2H) following an acute bout of resistance exercise both before (BEFORE) and after (AFTER) training. Leukocytes and NKCA were determined by flow cytometry and a whole blood (51)Cr release assay, respectively. RESULTS: Acute exercise increased total leukocyte (p < .05), CD8 (p < .05), CD4 (p < .05), and CD56 counts (p < .05), but there was no effect of training. NKCA was greater TR-AFTER-PRE (136%), -POST (80%), and -2H (127%) compared to similar values from TR-BEFORE (p < .05). CONCLUSION: Increased resting NKCA after chronic resistance training suggests that immunity has been improved.

Aged↗

PubMed2004

TLR4 is lower in resistance-trained older women and related to inflammatory cytokines.

INTRODUCTION/PURPOSE: Regular exercise may offset age-associated increases in inflammatory cytokines and reduce the risk of developing diseases with an inflammatory etiology by exerting "anti-inflammatory" effects. Toll-like receptor 4 (TLR4) signaling stimulates inflammatory cytokine production, and may explain the "anti-inflammatory" effect attributed to regular exercise. Therefore, the purpose of the present study was to compare the effect of acute (3 sets, 9 exercises, 10 repetitions at 80% of the 1-repetition maximum) and chronic resistance exercise on TLR4 and inflammatory cytokines. METHODS: Venous blood samples were collected from trained (TR, N = 10) and untrained (UT, N = 10) older (65-80 yr) postmenopausal women: before (PRE), immediately post (POST), and 2 h (2H), 6 h (6H), and 24 h (24H) after completion of exercise. Cell-surface expression of TLR4 (two-color immunofluorescent cytometry), LPS (25 microg x mL(-1))-stimulated cytokine production (ELISA), plasma cytokines (ELISA), and mRNA expression of TLR4 and cytokines (RT-PCR) were determined for each sample. RESULTS: TR had 124% less cell-surface TLR4 expression than UT (P < 0.05). A significant time effect was found for LPS-stimulated IL-6, IL-1beta, and TNF-alpha, where 6H was significantly greater than all other samples. No significant effects were found for plasma (IL-6 and TNF-alpha) or mRNA expression (IL-6, TNF-alpha, and IL-1beta) of inflammatory cytokines. When subjects were grouped according to cell-surface TLR4 expression (HI and LO), LPS-stimulated TNF-alpha (302%), IL-1beta (209%), and IL-6 (167%) production was greater for HI than LO (P < 0.05). CONCLUSION: Regularly exercising older women expressed less cell-surface TLR4 but did not have lower plasma levels or produce less LPS-stimulated inflammatory cytokines at rest or in response to a single bout of resistance exercise. TLR4 changes may explain the "anti-inflammatory" effect that has recently been attributed to chronic (2x wk for previous 24 months) resistance exercise training.

Adaptation, Physiological↗

PubMed2003

Carbohydrate intake during endurance exercise increases natural killer cell responsiveness to IL-2.

The purpose of this study was to evaluate the effect of high-intensity endurance exercise and carbohydrate consumption on in vitro responsiveness of natural killer (NK) to IL-2 (2.5 U/ml for 24 h). Thirteen male subjects (18-26 yr old; peak O2 consumption = 59.79 +/- 5.13 ml.kg-1.ml-1) were recruited to complete two 1-h (75-80% peak O2 consumption) cycling trials in a random counterbalanced order: carbohydrate (CHO) and placebo (Pla). Venous blood samples were collected before (Pre), immediately (Post), 2 h (2H), and 4 h (4H) after exercise. All resting samples were taken after 15 min of seated rest. NK (CD3-/56+), activated NK (CD3-/56+/69+), helper T cell (Th; CD3+/4+), and cytotoxic T cell (Tc; CD3+/8+) number were measured by using flow cytometry. NK cell activity (NKCA) was determined by using both a 51Cr release assay (NKCA-51) and activated NK cell number (NKCA-69). Immune system variables were not different between CHO and Pla, with the exception of NK cell responsiveness to IL-2, where Post (116.2%) and 4H (48.4%) was significantly greater in CHO (P < 0.05). NK, Th, and Tc were significantly higher Post (40.7, 102.7, and 82.0%, respectively) and lower at 2H (-51.9, -53.3, and -53.2%, respectively) than Pre (time effect). 4H was not different from Pre for NK, Th, and Tc. NKCA was significantly lower 2H (NKCA-51, NKCA-69) and 4H (NKCA-69) than Pre. CHO consumption during exercise did not prevent disruptions in unstimulated immune system function, but it did enhance NK responsiveness to IL-2.

Adolescent↗

PubMed2003

Toll-like receptor 4 and CD14 mRNA expression are lower in resistive exercise-trained elderly women.

The purpose of this study was to examine the influence of resistive exercise training and hormone status on mRNA expression of toll-like receptor 4 (TLR4), CD14, IL-1beta, IL-6, and TNF-alpha. Resistive exercise-trained women on "traditional" hormone replacements [hormone replacement therapy (HRT), n = 9], not taking hormones (NHR, n = 6), or taking medications known to influence bone (MIB, n = 7) were compared with untrained subjects not taking supplemental hormones (Con, n = 6). Blood was taken from trained subjects before, immediately after, and 2 h after resistive exercise (same time points for resting Con). TLR4 mRNA expression (RT-PCR) was not different among groups or across time but was significantly (P = 0.044) lower (1.9-fold) when trained groups were collapsed and compared with Con. There was also a significant group effect (P < 0.0001) for TLR4 mRNA when expressed per monocyte. CD14 expression was significantly (P = 0.006) lower (2.3-fold) for training groups collapsed and compared with Con. CD14 mRNA, expressed per monocyte, was significantly lower immediately after resistive exercise for NHR, HRT, and MIB compared with Con. There were few significant effects detected for IL-6, IL-1beta, and TNF-alpha mRNA, but there was a significant group effect (P < 0.0001) for TNF-alpha mRNA expressed per monocyte (Con > HRT, NHR, MIB). These findings suggest that there may be a resistive exercise training-induced reduction in TLR4/CD14 expression in older women. Further research is needed to determine whether lower TLR4/CD14 could explain the lower LPS-stimulated inflammatory cytokines observed in these women.

Aged↗

PubMed2003

Repeated endurance exercise affects leukocyte number but not NK cell activity.

INTRODUCTION/PURPOSE: The purpose of this study was to determine the affects of repeated bouts of exercise in the same day on circulating leukocyte number and NK cell activity (NKCA). METHODS: Ten males (18-25 yr of age) were chosen to complete four trials: two exercise bouts (TB), AM exercise (AM-EX), PM exercise (PM-EX), and control (CN) in a random, counter-balanced order. Exercise consisted of 1-h cycle ergometry, split into three, 20-min segments (5 min at 50% [V0](2peak) and 15 min at 70% [V0](2peak)), and was separated by a 4-h passive recovery. Blood samples were collected from a peripheral arm vein before, immediately, 2 h, and 24 h after the AM bout, and a second series was drawn for the PM bout. Leukocyte subpopulations were measured by manual counting using a hemacytometer and Wright-Giemsa-stained differential slides. NKCA was measured with a whole-blood 51Cr-release assay against K562 target cells. RESULTS Total leukocyte (13.2 +/- 1.2 x 109 L-1, P < 0.035) and neutrophil (7.6 +/- 0.7 x 109 L-1, P < 0.001) counts were significantly higher after two bouts of exercise than a single exercise bout completed in the morning (leukocyte: 7.8 +/- 0.7 x 109 L-1; neutrophil: 5.2 +/- 0.5 x 109 L-1) or afternoon (leukocyte: 9.9 +/- 0.8 x 109 L-1; neutrophil: 5.6 +/- 0.9 x 109 L-1). Lymphocyte counts were significantly greater (P < 0.001) after PM (4.2 +/- 0.5 x 109 L-1) than AM (3.7 +/- 0.4 x 109 L-1) exercise. NKCA was significantly greater (P < 0.001) after exercise in the afternoon (35.3 +/- 8.1%) than morning (27.2 +/- 5.9%). CONCLUSION: PM exercise produced a larger increase in NKCA than AM exercise, possibly indicative of an interaction between exercise and a diurnal effect. These data suggest two bouts of endurance exercise in 1 d produce an "additive effect" for total leukocyte and neutrophil counts. and to a lesser degree lymphocyte counts, but did not appear to impact shifts in NKCA.

Adolescent↗

PubMed2003

Exercise in hot and cold environments: differential effects on leukocyte number and NK cell activity.

INTRODUCTION: Exercise and environmental temperature have been reported to affect the immune system, but few studies have examined the combined effects of very hot or cold temperatures during exercise in the same group of subjects. Therefore, the purpose was to examine the immune responses following exercise combined with exposure to hot and cold environments. METHODS: There were 10 men who completed 2 60-min cycle ergometry (60% VO2peak) trials: hot (HT: 38 degrees C, 45% RH) and cold (CD: 8 degrees C, 50% RH). Rectal core temperatures (Tc), average skin temperatures (Tsk), and HR were recorded every 15 min of exercise. Venous blood was collected before (PRE), immediately after (POST), 2 h after (2 h), and 24 h after exercise (24 h). Physiologic strain index (PSI) was calculated. Total and differential leukocytes were determined by manual counting (adjusted for plasma volume shifts). Natural killer cell activity (NKCA) was determined by a whole blood 51Cr-release assay. RESULTS: Tsk, Tc, and PSI were significantly lower in the CD than HT trial (p < 0.05). Total leukocyte count was greater POST (40%) and 2 h (74%) than PRE and 24 h in both conditions (p < 0.05). Neutrophil count was greater POST (49%) and 2 h (132%) than PRE and 24 h in both conditions (p < 0.05). Lymphocyte count was greater POST (24%) in HT than CD (p < 0.05). NKCA was greater POST (38%) than PRE, 2 h, and 24 h in both conditions (p < 0.05). HT caused significant increases for Tc and Tsk above those observed for CD (p < 0.05). PSI was greater in HT (9.92 +/- 0.93) than CD (4.24 +/- 0.56) (p < 0.05). DISCUSSION: Exercise in HT produced more physiological stress than CD; however, this difference was not manifested in the immune system response. Heat and cold stress in combination with exercise produce similar disturbances in immunity during recovery from exercise.

Adult↗

PubMed2002

Effect of exercise, heat stress, and hydration on immune cell number and function.

PURPOSE: The purpose of this study was to determine the effect of thermal stress and hydration status on immune function during exercise. METHODS: Ten trained men completed four cycle ergometer rides at 55% VO2peak under the following conditions: EN (euhydrated neutral; 22 degrees C, 30% RH), DN (dehydrated neutral), EH (euhydrated hot; 38 degrees C, 45% RH), and DH (dehydrated hot). During EN and EH, a carbohydrate/electrolyte beverage was consumed at a rate matching sweat loss, and during DN and DH, no fluid was ingested. Blood samples were drawn pre- and postexercise, and at 2 and 24 h of recovery. Cell counts were determined by automated counting and flow cytometry. Neutrophil activity was assessed as superoxide production, lymphocyte function was determined via PHA-stimulated mitogenesis, and natural killer (NK) cell activity was measured with a 51Cr-release assay. Cortisol was assayed via RIA. RESULTS: Lymphocytes proliferation was depressed 2 h after exercise in all conditions (P < 0.05); however, when expressed on a per cell basis, function was greater in the DH and EH conditions. NK activity (max x 10(3) cells) was greater post compared with preexercise in all conditions (EH = 25.5 +/- 16.8, DH = 26.2 +/- 10.5, EN = 19.3 +/- 11.0, and DN = 16.5 +/- 8.7) but was not different between conditions. Leukocyte, neutrophil, lymphocyte, and NK cell counts were also elevated postexercise with the former two remaining elevated 2 h postexercise in the EH and DH conditions. Cortisol was greater postexercise in EH (22.1 +/- 1.3) and DH (27.7 +/- 1.3) compared with EN (17.8 +/- 2.1) and DN (18.9 +/- 1.6 microg x dL(-1). CONCLUSION: Euhydration did not affect cell number or function when compared with a dehydrated state; however, the hot environment caused more severe disturbances in these measures compared with a neutral environment.

Adult↗