Freewheel training decreases pro- and increases anti-inflammatory cytokine expression in mouse intestinal lymphocytes

Intestinal inflammation and inflammatory bowel diseases (IBD) may occur due to imbalances in pro- and anti-inflammatory cytokines. Long-term exercise reduces the risk for IBD. The purpose of this study was to determine the effect of long-term wheel running in healthy mice on intestinal lymphocyte (IL) expression of pro- and anti-inflammatory cytokine proteins. In addition, pro- and anti-apoptotic proteins and the percentage of early apoptotic, late apoptotic, and dead IL were measured with wheel running and following acute aerobic exercise. Female C57BL/6 mice were given 16 weeks of wheel running (WR) or a control condition (No WR) and at the end of training were assigned to a single acute treadmill exercise session with sacrifice immediately, 2 h after, or 24 h after completion of exercise, or were not run (sedentary) with respect to the acute treadmill exercise. Intestinal lymphocytes were assessed for pro-(TNF-α, IL-17) and anti-(IL-10) inflammatory, and pleiotropic (IL-6) cytokines, and pro-(caspase 3 and 7, AIF) and anti-(Bcl-2) apoptotic protein expression. The percent of early (Annexin⁺) and late (Annexin⁺PI⁺) apoptotic, and dead (PI⁺) IL was determined. WR mice had lower TNF-α and caspase 7, and higher IL-10 and IL-6 expression in IL than No WR mice. A single exposure to intense aerobic treadmill exercise increased pro-(TNF-α) and anti-(IL-10) inflammatory cytokine and pro-apoptotic protein (caspase 3) expression in IL. The percent of early and late apoptotic, and dead IL were higher after acute exercise. Although long-term voluntary wheel running did not protect against acute exercise-induced changes in IL cytokine expression or apoptosis, there was an overall ‘anti-inflammatory’ effect observed as a result of wheel running in healthy mice.     

Effect of repeated exercise stress on caspase 3, Bcl-2, HSP 70 and CuZn-SOD protein expression in mouse intestinal lymphocytes

The purpose of this study was to characterize the expression of apoptosis (caspase 3, Bcl-2) and survival (HSP 70, antioxidant CuZn-SOD) proteins in intestinal lymphocytes (IL) of mice after repeated exercise stress. Plasma corticosterone concentration was greater than twofold higher immediately after exercise compared with the non-exercised condition. IL numbers decreased 24 h after cessation of exercise (p<0.05); this was associated with increased caspase 3 (p<0.05), HSP 70 (p<0.001) and CuZn-SOD (p<0.05) expression in IL immediately after exercise relative to IL from non-exercised mice. Expression of these proteins returned to control levels 24 h after the cessation of exercise stress.     

Intravenous catecholamine administration affects mouse intestinal lymphocyte number and apoptosis

The purposes of this study were to determine plasma and intestinal epinephrine (E) and norepinephrine (NE) concentrations in mice after exercise stress and, the effect of intravenous injection of E and NE (at concentrations during exercise) on viability of intestinal lymphocytes (IL). Exhaustive exercise significantly elevated plasma E and NE, and intestinal E, compared with sedentary animals. Twenty-four hours after intravenous NE administration, IL counts were higher (p<0.001) and % apoptotic IL were lower (p<0.001) than saline conditions. E resulted in fewer apoptotic IL at 24 h compared to saline controls. E and NE differentially influence IL numbers at 24 h after injection although both result in fewer % apoptotic IL relative to mice given saline only.     

Freewheel running selectively prevents mouse CD4+ intestinal lymphocyte death produced after a bout of acute strenuous exercise

Aerobic exercise increases oxidant stress and leads to apoptosis of mouse intestinal lymphocytes (IL). The purpose of this study was to determine whether freewheel running prevents IL loss 24 h after a bout of strenuous exercise. Mice were randomly assigned to in-cage running wheels with 24 h access (WR) or individual cages without running wheels (NR) for 4 months. WR mice accumulated 364 km over 4 months and had higher cytochrome oxidase activity in the plantaris (p < .05), indicative of training. Total intestinal, CD3alphabeta, CD3gammadelta, CD8alpha, and CD8beta lymphocytes and intracellular glutathione were significantly lower in WR and NR mice 24 h post-exercise. The number of CD4 IL decreased 24 h after exercise in NR (p < .01) but not in WR mice relative to their respective no exercise controls. Thus, freewheel running in mice for 4 months prevented CD4 IL loss after acute exercise.     

Cytokine activity contributes to induction of inflammatory cytokine mRNAs in spinal cord following contusion

Injury of the spinal cord leads to an inflammatory tissue response, probably mediated in part by cytokines. Because a common therapy for acute spinal cord injury is the use of an antiinflammatory synthetic glucocorticoid (methylprednisolone), we sought to determine mechanisms contributing to inflammation shortly after acute injury. Cytokine mRNAs [interleukin (IL)-1alpha, IL-1beta, tumor necrosis factor (TNF)-alpha, and IL-6] were increased during the first 2 hr following weight-drop compression injury by RNase protection assay, prior to the reported appearance of circulating lymphocytes. This immediate pattern of cytokine mRNA induction could be replicated in cultured, explanted spinal cord slices but not in whole blood of injured animals, which is consistent with a tissue source of cytokine mRNAs. Western blotting detected IL-1beta-like immunoreactivity released into culture medium following explantation and pro-IL-1beta-like immunoreactivity in freshly dissected spinal cord tissue. Pharmacologically blocking IL-1 and TNF-alpha receptors significantly reduced expression of IL-1alpha, IL-1beta, and TNF-alpha mRNAs. Finally, mice lacking both IL-1 and TNF-alpha receptors exhibited diminished induction of TNF-alpha, IL-6, and IL-1ra mRNAs following injury. Therefore, we conclude that contusion injury induces an immediate release of cytokines, which then contributes to the induction of cytokine mRNAs.     

Interleukin-10 correlates with oxidized low density lipoprotein in coronary culprit plaques

Inflammation and oxidation play crucial roles in plaque instability. We immunohistochemically assessed expression of the anti-inflammatory cytokine interleukin (IL)-10, and of oxidized low density lipoprotein (ox-LDL) in coronary atherectomy specimens from 19 and 18 patients with stable and unstable angina, respectively. Immunopositive areas for IL-10 and ox-LDL were significantly greater in the group with unstable angina (p < 0.05, each), and they positively correlated (r = 0.452, p < 0.005). These results suggest that IL-10 plays an anti-inflammatory role in atherosclerotic lesions and modulates the inflammatory process in unstable coronary plaque.

Conflict of interest

None     

IL-10 and glucocorticoids inhibit Abeta(1-42)- and lipopolysaccharide-induced pro-inflammatory cytokine and chemokine induction in the central nervous system

Alzheimer's disease (AD) is characterized by neuropil threads composed of structurally abnormal neurites, neurons containing paired helical filaments of tau protein, and extracellular deposits of amyloid-beta (Abeta) peptide, a protein fragment having neurotoxic and glial immune response activating potential. In the present study, we demonstrate that an acute intracerebroventricular (icv) injection of Abeta(1-42) in the mouse induces a time- and dose-dependent production of IL-1alpha, IL-1beta, IL-6 and MCP-1 in the hippocampus and cortex as measured by ELISA. Cytokine and chemokine levels were maximal at 9 h, with MCP-1 and IL-1alpha remaining elevated over a 24 h period and IL-1beta remaining elevated over a 48 h period. The temporal profile of Abeta-induced cytokine induction differed from that observed for LPS. Following an icv injection of LPS, maximal levels of IL-1alpha, IL-1beta, IL-6 and MCP-1 were attained by 9 h and, except for MCP-1, returned to levels indistinguishable from control at 24 h. MCP-1 remained elevated at 24 h and returned to basal levels at 48 h. In contrast, little production of TNF-alpha was observed under either Abeta or LPS acute stimulus conditions. Treatment with anti-inflammatory agents such as prednisolone, dexamethasone, or IL-10 inhibited both Abeta- and LPS-induced cytokine and chemokine production in the brain. In summary, icv administration of Abeta and LPS induced elevated brain levels of pro-inflammatory cytokines that could be inhibited by immune suppressing drugs and anti-inflammatory proteins, thus providing support for the utility of anti-inflammatory therapeutics in modulating the immunopathology observed in brain inflammatory diseases such as AD.     

Vasoactive intestinal peptide can modulate immune and endocrine responses during lipopolysaccharide-induced acute inflammation

OBJECTIVES: In many studies, it has been reported that vasoactive intestinal peptide (VIP) may play an important role in modulation of the immunological response. VIP can be produced by immunological cells, and also the receptors for this neuropeptide are present in many of these cells. The aim of our study was to estimate the effects of the administration of exogenous VIP on serum concentrations of proinflammatory cytokines [interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha] and an anti-inflammatory cytokine (IL-10) during lipopolysaccharide (LPS)-induced acute inflammation. We also estimated the influence of VIP on pituitary [FSH, LH, TSH and prolactin (PRL)], thyroid (T3 and T4), adrenal (corticosterone) and gonadal (testosterone) hormones in response to LPS-induced acute inflammation. METHODS: Male Wistar-Kyoto rats were divided into four groups, which received, respectively, placebo (0.9% NaCl), LPS, VIP and VIP with LPS. The TNF-alpha and IL-6 serum concentrations were measured after 2 h from the time of the administration of the agents, IL-10 was measured after 4 h, and the pituitary, thyroid, adrenal and gonadal hormone concentrations were measured after 2 and 4 h. Cytokine concentrations were estimated using ELISA tests, and hormone concentrations were measured using RIA tests. RESULTS: In our experiments, LPS administration dramatically increased serum proinflammatory cytokine concentrations (TNF-alpha and IL-6) after 2 h and the anti-inflammatory cytokine (IL-10) after 4 h, as well as increasing the serum corticosterone concentration (after 2 and 4 h) and LH (after 2 h). LPS application decreased serum concentrations of T3 and TSH (both after 2 h), testosterone (after 2 and 4 h), FSH after 4 h and PRL after 4 h. VIP administration decreased the serum IL-10 concentration after 4 h and T3 concentration after 2 h and increased serum concentrations of FSH and corticosterone after 4 h. VIP administrated simultaneously with LPS decreased the LPS-induced increase in IL-6 and corticosterone concentrations (consecutively after 2 and 4 h). VIP also enhanced LPS-induced thyroid hormone (T3 and T4) suppression after 4 h and testosterone suppression after 4 h. CONCLUSION: We conclude that VIP can modulate not only immune responses but also hormonal responses during acute inflammation.     

Acute stress suppresses pro-inflammatory cytokines TNF-alpha and IL-1 beta independent of a catecholamine-driven increase in IL-10 production

Interleukin (IL)-10 is an anti-inflammatory cytokine that can down-regulate various aspects of the immune response. In this study we demonstrate that exposure to a psychophysiological stressor (swim stress) increases IL-10 production in female rats in response to an in vivo challenge with bacterial lipopolysaccharide (LPS). This increase in LPS-induced IL-10 was associated with suppression of the pro-inflammatory cytokines IL-1beta and TNF-alpha, indicating that overall, swim stress promotes an immunosuppressive cytokine phenotype. Despite the well-documented ability of IL-10 to suppress pro-inflammatory cytokine production, neutralisation of IL-10 failed to block the stress-induced suppression of IL-1beta and TNF-alpha. These data indicate that the suppressive effect of swim stress on these pro-inflammatory cytokines occurs independently of increased IL-10 production. To determine if swim stress-induced immunosuppression was mediated by increased sympathetic nervous system activity, and subsequent beta-adrenoceptor activation, we assessed the ability of the beta-adrenoceptor antagonist nadolol to block stressor-induced changes in cytokine production. Whilst pre-treatment with nadolol completely blocked the stress-induced increase in IL-10, it failed to alter the suppression of TNF-alpha or IL-1beta. Similarly, pre-treatment with the glucocorticoid receptor antagonist mifepristone also failed to attenuate the suppressive effect of swim stress on IL-1beta and TNF-alpha production. These data indicate that neither increased glucocorticoid secretion, nor catecholamine-induced beta-adrenoceptor activation, mediates the suppressive effect of swim stress on pro-inflammatory cytokine production. Taken together, these data demonstrate a role for beta-adrenoceptor activation in the ability of acute swim stress to increase LPS-induced IL-10 production, and also highlight a mechanistic dissociation between the ability of swim stress to increase IL-10 and suppress pro-inflammatory cytokine production.     

The d-alanine content of lipoteichoic acid is crucial for Lactobacillus plantarum-mediated protection from visceral pain perception in a rat colorectal distension model

Abstract  The mechanisms leading to positive effects of probiotics in irritable bowel syndrome and inflammatory bowel disease have not been clarified, but the possible involvement of cell wall components is widely discussed. Reduction of the d -alanine content of lipoteichoic acid (LTA) in Lactobacillus plantarum (Dlt ⁻ mutant) enhanced its anti-inflammatory properties in a mouse colitis model. Another lactobacillus species inhibited visceral pain perception in response to colorectal distension (CRD) in rats. Therefore, we investigated if LTA modification influences the constitutive intestinal pain perception in addition to modulation of cytokine release. Male Sprague-Dawley rats were gavaged with L. plantarum , L. plantarum Dlt ⁻ mutant or buffer control, respectively and the responses to CRD were tested in this non-inflammatory model. Tumour necrosis factor (TNF), interferon (IFN)-gamma and interleukin (IL)-10 release were measured in colon tissue homogenates and upon anti-CD3/CD28 activation of isolated splenocytes and mesenteric lymphocytes. Control animals showed significant bradycardia following noxious CRD, whereas only the L. plantarum Dlt ⁻ mutant inhibited the response. The mutant also decreased the activation-induced release of TNF and IFN-gamma from mesenteric T cells and the IL-10 concentration in colonic tissue, while increasing the activation-induced secretion of IL-10 in splenocytes and mesenteric lymphocytes and the baseline IL-10 release of splenocytes. In conclusion, d -alanine depletion of LTA in L. plantarum inhibited visceral pain perception in healthy, non-inflamed rats. Regardless of the non-inflammatory nature of the model decreased visceral pain perception was seen in parallel with anti-inflammatory properties.     

Disturbed in vitro adrenergic modulation of cytokine production in inflammatory bowel diseases in remission

OBJECTIVE: Psychological stress has been implicated in the pathophysiology of both inflammatory and functional gastrointestinal (GI) diseases. The goal of this study was to address neuroendocrine modulation of cytokine production by peripheral blood cells in GI diseases. METHODS: We analyzed the in vitro effects of the beta-adrenergic agonist terbutaline and the glucocorticoid agonist dexamethasone on TNF-alpha and IL-10 production by LPS-stimulated monocytes in whole cell blood cultures in patients with inflammatory bowel diseases in remission (N=10), diarrhoea-predominant irritable bowel syndrome (IBS, N=12), patients with a recent gastroenteritis (post-infectious group, N=10), and healthy controls (N=15). RESULTS: In response to terbutaline, there was a significant increase in IL-10 production (concentration effect: p<0.05), which was diminished in IBD (group effect: p<0.01), comparable in IBS and controls, but enhanced in the post-infectious group (group x concentration effect: p<0.05). In contrast, terbutaline resulted in a concentration-dependent suppression of TNF-alpha production, which was comparable in all groups. Dexamethasone suppressed TNF-alpha production in a dose-dependent manner in all groups, but this effect was significantly more pronounced in post-infectious subjects (group effect: p<0.05). CONCLUSIONS: In IBD, disturbed adrenergic regulation of IL-10 could be part of the mechanism(s) underlying the modulation of disease activity by psychological stress. Diarrhoea-predominant IBS was not associated with altered adrenergic or glucocorticoid regulation of cytokine production by peripheral blood cells, whereas a recent history of gastroenteritis was associated with disturbed neuroendocrine modulation of cytokine production, which may play role in the pathophysiology of post-infectious IBS.     

Strenuous physical exercise adversely affects monocyte chemotaxis

Physical exercise is important for proper cardiovascular function and disease prevention, but it may influence the immune system. We evaluated the effect of strenuous exercise on monocyte chemotaxis. Monocytes were isolated from blood of 13 young, healthy, sedentary individuals participating in a three-week training program which consisted of repeated exercise bouts. Monocyte chemotaxis and serological biomarkers were investigated at baseline, after three weeks training and after four weeks recovery. Chemotaxis towards vascular endothelial growth factor-A (VEGF-A) and transforming growth factor-β1 (TGF-β1) was completely inhibited immediately after training (p<0.01), and remained so after four weeks recovery. Likewise, monocyte chemoattractant protein-1 (MCP-1)-induced migration declined after training (p<0.01) and improved only partially during the recovery period. MCP-1 serum levels were significantly reduced after four weeks recovery compared to baseline (p<0.01). Total blood antioxidant capacity was enhanced at this time point (p<0.01). Monocyte chemokinesis, TGF-β1 and nitric oxide serum levels remained unchanged during the study. Strenuous three-week training consisting of repeated exercise bouts in healthy, sedentary individuals reduces monocyte chemotaxis. It remains to be established, whether this is a sound adaptation to increased stimuli or an untoward reaction to overtraining. Nevertheless, the effect remains for several weeks with no exercise.     

Glycoursodeoxycholic acid and interleukin-10 modulate the reactivity of rat cortical astrocytes to unconjugated bilirubin

The pathogenesis of bilirubin encephalopathy seems to result from accumulation of unconjugated bilirubin (UCB) within the brain. We have recently demonstrated that UCB causes astroglial release of proinflammatory cytokines and glutamate, as well as cell death. The bile acid glycoursodeoxycholic acid (GUDCA) and the anti-inflammatory cytokine interleukin (IL)-10 have been reported to modulate inflammation and cell survival. In this study we investigated the effect of these therapeutic agents on the astroglial response to UCB. Only GUDCA prevented UCB-induced astroglial death. The secretion of tumor necrosis factor-alpha (TNF-alpha) and IL-1beta elicited by UCB in astrocytes was reduced in the presence of GUDCA and IL-10, whereas the suppression of IL-6 was only counteracted by GUDCA. Neither GUDCA nor IL-10 modulated the accumulation of extracellular glutamate. Additionally, IL-10 markedly inhibited UCB-induced nuclear factor-kappaB nuclear translocation and cytokine mRNA expression, whereas GUDCA only prevented TNF-alpha mRNA expression. Moreover, GUDCA inhibited TNF-alpha- and IL-1beta-converting enzymes, preventing the maturation of these cytokines and their consequent release. Collectively, this study shows that IL-10 action is restricted to UCB-induced release of TNF-alpha and IL-1beta from the astrocytes, whereas GUDCA presents a more ubiquitous action on the astroglial reactivity to UCB. Hence, GUDCA may have potential benefits over an IL-10 therapeutic approach in reducing UCB-induced astrocyte immunostimulation and death.     

Chronic administration of tianeptine balances lipopolysaccharide-induced expression of cytokines in the spleen and hypothalamus of rats

The antidepressant tianeptine has been shown to protect the hippocampus against the deleterious consequences of stress and to attenuate the behavioral and neuroendocrine effects of the cytokine inducer lipopolysaccharide (LPS). Since sickness symptoms are linked to peripheral and brain production of cytokines and pro-inflammatory cytokines can promote neurotoxicity, the present study was undertaken to test the possibility that tianeptine attenuates production of pro-inflammatory cytokines. This hypothesis has been tested by studying the effects of a chronic intraperitoneal (i.p.) administration of tianeptine (10 mg/kg twice a day for 21 days) to rats on the induction by LPS (250 microg/kg, i.p.) of the production of pro- and anti-inflammatory cytokines, at the periphery (spleen, pituitary) and in the brain (hypothalamus, hippocampus). The expression of mRNAs coding for IL-1 beta, TNF-alpha, IL-6 or IL-10 (RT-PCR) and plasma levels of IL-1 beta, TNF-alpha and IL-10 (ELISA) were measured at various time intervals following LPS. Chronic tianeptine treatment attenuated LPS-induced expression of TNF-alpha in the spleen as well as plasma levels of this cytokine and altered the central balance between pro- and anti-inflammatory cytokines (IL-1 beta/IL-10). These results open new vistas in the pharmacological activity of tianeptine and provide further insights on the possible mechanisms of action involved in its neuroprotective properties.     

High levels of IL-10 secreting cells are present in blood in cerebrovascular diseases

Ischemic stroke is associated with altered systemic immune responses both early after the onset and in the recovery phase. Interleukin (IL)-10, a Th2 related cytokine, has multiple effects on different cell types, including T and B lymphocytes, monocytes, neutrophils and mast cells. IL-4 is another Th2 cytokine that inhibits the synthesis of pro-inflammatory cytokines by Th1 clones. We used enzyme-linked immunospot assays to detect and enumerate blood mononuclear cells (MNC) secreting IL-10 and IL-4 spontaneously as well as after stimulation with myelin basic protein (MBP), considered to be an autoantigen of possible pathogenic importance in, for example, multiple sclerosis, to evaluate the involvement of anti-inflammatory cytokines in ischemic stroke. All patients with ischemic stroke and cerebral hemorrhage had strongly elevated numbers of IL-10 secreting blood MNC compared with healthy individuals. Numbers of MBP-reactive IL-10 secreting blood MNC were also elevated in a proportion of the patients with stroke and hemorrhage. Levels of IL-4 secreting blood MNC did not differ in ischemic stroke versus healthy individuals. The anti-inflammatory IL-10 could play a pivotal role in ischemic stroke as well as cerebral hemorrhage.     

Heat stress, cytokines, and the immune response to exercise

To examine the effect of exercise and heat stress on cytokine production, seven males (77 +/- 2 kg; VO(2peak) = 4.7 +/- 0.4 L min(-1)) completed two (15 degrees C; CON or 35 degrees C; HEAT) 90 min cycling trials at 70% VO(2peak). Blood samples were collected throughout and analysed for spontaneous, and LPS-stimulated intracellular monocyte cytokine production, plasma cytokine levels, and circulating stress hormone concentration. Plasma epinephrine, norepinephrine, and cortisol concentration were elevated (P < .05) as a result of exercise in CON. HEAT increased (P < .05) epinephrine and norepinephrine levels, however, cortisol concentration was not different between the two trials. Exercise had no effect on the concentration of circulating monocytes spontaneously producing IL-6, TNF-alpha or IL-1alpha, however, there was a decrease in the amount of TNF-alpha per cell post-compared with pre-exercise. HEAT had no effect on spontaneous intracellular cytokine production. Circulating levels of both IL-6 and TNF-alpha were elevated in HEAT, but not in CON. Upon stimulation with LPS, the concentration of monocytes positive for IL-6, TNF-alpha, and IL-1alpha production was elevated (P < .01) post- and 2 h post-compared with pre-exercise. Stimulated cells, however, produced less (P < .05) TNF-alpha post-exercise and less (P < .05) TNF-alpha and IL-6 2 h post-exercise. HEAT resulted in an increase (P < .05) in the concentration of stimulated cells positive for TNF-alpha and IL-1alpha, however, did not affect the amount of cytokine produced by stimulated monocytes. These results demonstrate that exercise decreases the amount of cytokine produced by LPS-stimulated monocytes, possibly due to elevated levels of circulating stress hormones. Heat stress did not, however, augment the suppression in the amount of cytokine produced by circulating monocytes upon stimulation, despite elevated catecholamines.     

Effects of phosphodiesterase inhibitors on cytokine production by microglia.

Type III and IV phosphodiesterase inhibitors (PDEIs) have recently been shown to suppress the production of TNF-alpha in several types of cells. In the present study, we have shown that all the types of PDEIs, from type I- to V-specific and non-specific, suppress the production of TNF-alpha by mouse microglia stimulated with lipopolysaccharide (LPS) in a dose-dependent manner. Certain combinations of three different types of PDEIs synergistically suppressed TNF-alpha production by microglia at a very low concentration (1 microM). Since some PDEIs reportedly pass through the blood-brain barrier (BBB), the combination of three PDEIs may be worth trying in neurological diseases, such as multiple sclerosis and HIV-related neurological diseases in which TNF-alpha may play a critical role. Some PDEIs also suppressed interleukin-I (IL-I) and IL-6 production by mouse microglia stimulated with LPS. In contrast, the production of IL-10, which is known to be an inhibitory cytokine, was upregulated by certain PDEIs. The suppression of TNF-alpha and induction of IL-10 were confirmed at the mRNA level by RT-PCR. PDEIs may be useful anti-inflammatory agents by downregulating inflammatory cytokines and upregulating inhibitory cytokines in the central nervous system. (CNS).     

Long-term effects of mild exercise on intraocular pressure in athletes and sedentary subjects

The long-term effects of acute submaximal exercise on intraocular pressures (IOPs) of right-and left-eyes and recovery times to basement levels of IOP in postexercise periods in sedentary and physically fit subjects were investigated. Twenty-five sedentary and 24 physically fit subjects, ranging in age 17 to 22 years, participated. Intraocular pressures were measured by a pneumotonometer. Measurements were taken in the morning at about nine (at rest) and immediately, 30 min and 2 h after acute submaximal exercise. In sedentary subjects, IOPs of both right- and left-eyes decreased immediate after exercise, but, these decreases in both eyes continued 30 min and 2 h after exercise. In physically fit subjects, IOPs of both right- and left-eyes increased immediate after exercise, but decreased after 30 min exercise compared to basement levels, and this decrease continued 2 h after exercise. Acute submaximal exercise decreased IOPs of right and left eyes over a period 2 h in sedentary and physically fit subjects. IOP reducing after exercise was different between right- and left-eyes in sedentary subjects. These results suggest that exercise can be used in ocular hypertension treatment.