The effect of sodium bicarbonate on cytokine secretion in CKD patients with metabolic acidosis.

The incidence of acidosis increases with the progression of chronic kidney disease (CKD). Correction of acidosis by sodium bicarbonate may slow CKD deterioration. Inflammation, which is common in CKD, may be related to acidosis. Whether the slower rate of GFR decline following the correction of acidosis is related to changes in inflammatory markers is unknown. The current study examined whether correcting CKD-acidosis affected inflammatory cytokines secretion. Thirteen patients with CKD 4-5 and acidosis were tested for cytokines secretion from peripheral-blood mononuclear cells at baseline and after one month of oral sodium bicarbonate. Following treatment with sodium bicarbonate there was no change in weight, blood pressure, serum creatinine, albumin, sodium, calcium, phosphate, PTH, hemoglobin and CRP. Serum urea decreased (134±10-116±8 mg/dl, P=0.002), potassium decreased (5.1±0.4-4.8±0.1 mequiv./l, P=0.064), pH increased (7.29±0.01-7.33±0.01, P=0.008), and serum bicarbonate increased (18.6±0.4 mequiv./l to 21.3±0.3 mequiv./l, P=0.001). The secretion of the anti-inflammatory cytokine IL-10 decreased (2.75±0.25 ng/ml to 2.29±0.21 ng/ml, P=0.041). There was no significant change in the secretion of the other pro-inflammatory and anti-inflammatory cytokines, including IL-1ß, IL-2, IL-6, TNFα, IFNγ, IL-1ra. Thus, correcting acidosis in CKD with bicarbonate decreases IL-10 secretion. Its significance needs to be further investigated.

Prolonged international normalized ratio during the first year of warfarin treatment.

OBJECTIVE: Oral anticoagulants (OAC) are effective in the prevention of thromboembolic events but are underused. The 1st year following the beginning of vitamin K antagonists is associated with higher bleeding rate, especially in patients with international normalized ratio (INR) of >4, leading to discontinuation of OAC. We hypothesized that the decision to discontinue OAC during the 1st year in patients with events of overanticoagulation is not fully justified. SETTING: A retrospective study of the association between warfarin overanticoagulation during the 1st year of treatment and the outcome and complications in patients admitted to an internal medicine department with INR>4. SUBJECTS: A cohort of 249 patients was divided according to OAC treatment duration: ≤12 months (group I, n=72; mean age, 79.1 years) and >12 months (group II, n=177; mean age, 78.3 years). RESULTS: International normalized ratio upon admission was higher in group I (INR, 6.88 versus 6.16; P=0.003). Patients in group I were overanticoagulated for a longer period (46.4% versus 18.5%; P<0.001) but had lower time in therapeutic range (39.0% versus 60.2%; P=0.001). The frequency of INR monitoring was higher in group I. The incidence of major and minor bleeding events and survival was similar. CONCLUSIONS: Patients who are admitted with INR>4 during the 1st year of OAC therapy are overanticoagulated for a longer period, have lower time in therapeutic range, but do not present with higher incidence of bleeding events, all compared with patients treated for longer than 12 months. Stricter INR monitoring and careful patient selection may prevent the discontinuation of OAC.

Do androgen deprivation drugs affect the immune cross-talk between mononuclear and prostate cancer cells?

The aim of the study was to examine the effect of androgen deprivation drugs, i.e. leuprolide and bicalutamide on the immune cross-talk between human peripheral blood mononuclear cells (PBMC) and cells from PC-3 and LNCaP human prostate cancer lines. PBMC, PC-3 and LNCaP were separately incubated without and with two androgen-deprivation drugs, i.e. leuprolide and bicalutamide, and the secretion of IL-1ß, IL-6, IL-1ra and IL-10 was examined. In addition, the effect of both drugs on the production of those cytokines was carried out after 24 hours incubation of PBMC with both types of cancer cells. Leuprolide or bicalutamide did not affect the production of the cytokines by PBMC or by the prostate cancer cells from the two lines. Incubation of PBMC with PC-3 or LNCaP cells caused increased production of IL-1ß, IL-6 and IL-10 as compared with PBMC incubated without malignant cells. While 10(-7) M and 10(-8) M of leuprolide caused a decreased secretion of IL-1ß by PBMC previously incubated with prostate cancer cells without the drug, bicalutamide did not affect this PBMC activity at any drug concentration. This observation suggests the existence of an additional mechanism explaining the effect of androgen deprivation therapy in prostate cancer patients.

Cytokine secretion and markers of inflammation in relation to acidosis among chronic hemodialysis patients.

BACKGROUND: Various cytokines are increased in hemodialysis (HD) patients, and are considered prognostic markers. Metabolic acidosis is common among chronic HD patients and is associated with survival. The relationship between acidosis and cytokines in HD patients has not been fully explored. The study aim was to measure pro- and anti-inflammatory cytokines in HD patients, with relation to bicarbonate levels. METHODS: Forty-seven stable HD patients were included (male/female 28/19, mean age 70.4 ± 14.5 years). Blood tests were taken before a midweek dialysis session. Cytokine secretion from peripheral blood mononuclear cells was measured. RESULTS: Acidosis versus no acidosis (serum HCO3 ­ 21.5 ± 0.2 vs. 24.9 ± 0.3 mEq/l, p < 0.001) was associated with decreased secretion of the anti-inflammatory interleukin-10 (IL-10, 1.16 ± 0.11 vs. 1.71 ± 0.20 ng/ml, p = 0.023). Patients with acidosis had higher parathyroid hormone (PTH), calcium-phosphate product, protein intake and transferrin. Higher IL-10 was associated with increased IL-6 secretion, higher bicarbonate, younger age and lower PTH. CONCLUSIONS: In stable chronic HD patients, a possible direct relation exists between metabolic acidosis and IL-10.

Regression of left ventricular hypertrophy in patients with primary aldosteronism/low-renin hypertension on low-dose spironolactone.

BACKGROUND: The incidence of left ventricular hypertrophy (LVH) in primary aldosteronism (PA) is higher than in essential hypertension. LVH is an independent cardiovascular risk factor. Treatment of PA with mineralocorticoid receptor blockers (MRBs) improves LVH. Previous studies included relatively small groups, low incidence of LVH and used high MRB dose. We tested the hypothesis that long-term regression of LVH in PA/low-renin hypertension may be achieved with low-dose MRB. METHODS: Forty-eight patients (male/female 28/20, age 61.4 years, range 47-84) had PA (low renin, high aldosterone and high aldosterone/renin ratio, n=24) or low-renin hypertension (low renin, normal aldosterone and high aldosterone/renin ratio, n=24). All had either LVH or concentric remodelling. All had an echocardiogram both at baseline and at 1 year after the initiation of spironolactone. A subgroup of 29 patients had an echocardiogram at baseline, 1 year (range 0.5-1.5) and 3 years (range 1.8-7). RESULTS: At baseline, spironolactone was commenced in all patients. The dose was 33.3±13.7 and 29.0±11.7 mg/day at 1 year and 3 years, respectively. A total of 73% of the patients received ≤37.5 mg/day. Introduction of spironolactone enabled the reduction of other antihypertensive medications (from 2.6±1.2 to 1.5±1.0 at 1 year). At 1 year, systolic and diastolic blood pressure decreased (149.3±14.1 to 126.2±12.0 mmHg, P<0.001, and 88.2±9.8 to 78.3±7.1 mmHg, P<0.001, respectively). At baseline, LVH was present in 39 of the 48 (81%) patients, and concentric remodelling, i.e. increased relative wall thickness (RWT) with a normal left ventricular mass index (LVMI), in 36 (75%). At 1 year, LVMI decreased in 44 of the 48 (92%) patients (142.9±25.4 versus 117.7±20.4 g/m2, P<0.001). LVH normalized in 16 of the 39 (41%) patients. RWT normalized in 36% of the patients. The changes in blood pressure and LVMI did not correlate. At 3 years, LVH decreased further and normalized in 57% of the patients. CONCLUSIONS: In patients with PA/low-renin hypertension, long-term regression of LVH may be achieved with low-dose MRB.

Expression of cyclin E in stage III colorectal carcinoma.

Carcinogenesis is characterized by an abnormal regulation of the cell cycle. Regulators of the cell cycle such as cyclin E play an important role in neoplasia and may be correlated with prognosis. The clinical significance of the expression of cyclin E in stage III colorectal carcinoma has not yet been investigated. The expression of cyclin E was evaluated in 49 patients. Using a multivariate analysis, the expression of cyclin E in the tumor at diagnosis was compared with various clinicopathological variables, including age, gender, tumor site, tumor size, tumor differentiation and lymph node involvement. There were more node-positive cases in the cyclin E-negative group than in the cyclin E-positive group (P=0.003). However, there was no correlation between the degree of cyclin E expression and the clinical data. In conclusion, our data suggest that overexpression of cyclin E does not predict the clinical outcome in colorectal cancer stage III. Negative cyclin E staining may be associated with lymph node involvement.

Resveratrol affects the cross talk between immune and colon cancer cells.

Resveratrol, a natural polyphenolic compound found mainly in grapes and their seeds, is gaining a widespread appreciation as a therapeutic adjuvant in a variety of diseases including cancer prevention. We examined the effect of resveratrol as a modulator of the immune dialog between peripheral blood mononuclear cells and those from two human colon carcinoma lines, expressed by a possible alteration of cytokine production. Resveratrol, incubated with non-stimulated mononuclear cells, caused a certain reduction of IL-6, IL-1ra and IL-10, and a moderate increase of TNFα release. On the other hand, resveratrol did not affect cytokine production by cancer cells from both lines. When resveratrol was added to immune and cancer cells jointly, an altered dose-dependent decreased production of the examined cytokines was obtained. These results favor the existence of a mechanism, additional to those already described, that may explain the preventive effect of resveratrol on tumorigenesis.

A study of elderly adults taking warfarin admitted with prolonged international normalized ratio: a community hospital's experience.

OBJECTIVES: To assess bleeding complications and outcome of individuals receiving oral anticoagulants who were admitted to the hospital with an international normalized ratio (INR) greater than 4 by comparing them according to age (≤ 80, >80). DESIGN: Retrospective cohort study. SETTING: Community hospital. PARTICIPANTS: All individuals (N = 253) admitted to the Department of Internal Medicine over a period of 4 years with an INR greater than 4: Group I, aged 80 and younger (n = 127); Group II, older than 80 (n = 126). Data included bleeding complications, survival, and quality of INR control before admission and up to 48 months after admission. RESULTS: Atrial fibrillation was the most common indication for warfarin therapy. Its incidence was higher in the older group (88% vs 73%, P = .004). More elderly participants lived in nursing homes (23% vs 9.4%. P = .004) or received in-home assistance (38.9% vs 20.5%, P = .002). There was no difference in INR upon admission, duration of warfarin treatment, or frequency of INR tests before admission. The incidence of bleeding events was 18.1% in Group I and 12.7% in Group II (P = .30). Major bleeding events occurred in 1.6% of Group I and none of Group II (P = .50). During follow-up after the first admission, the incidence of INR greater than 4 was higher in Group II (87.3% vs 70%, P = .02), without a difference in the number of additional admissions or bleeding events. CONCLUSION: Primary care physicians can safely maintain warfarin treatment in elderly adults, even in those with a history of hospitalization for high INR, using frequent INR measurements.

Human prostate cancer cells induce inflammatory cytokine secretion by peripheral blood mononuclear cells.

A substantial number of studies provide evidence that inflammation may play a significant role in the pathogenesis of prostate cancer via increased activity of inflammatory cytokines, particularly IL-6. We have previously shown that peripheral blood mononuclear cells (PBMC) are capable of carrying out an in vitro "immunomodulatory dialog" with colon cancer cells expressed by an increased production of pro-inflammatory cytokines by PBMC. The aim of the current study was to examine the model of cell-to-cell interaction between PBMC and prostate cancer cells from two lines - androgen resistant (PC-3) and androgen-dependent (LNCaP). For that purpose, cancer cells from both lines were incubated with PBMC, and cytokine secretion by PBMC was evaluated. The results showed a cell-concentration dependent increase in secretion of the pro-inflammatory cytokine IL-6 by PBMC induced by cells from both lines, whereas generation of IL-1ß and the anti-inflammatory cytokine IL-10 were found to be increased after incubation with PC-3 cells only. The secretion of IL-10 was slightly lower following incubation of PBMC with supernatants derived from PC-3 cells. The results of the study support the possibility that prostate cancer cell-induced cytokine production by PBMC, and particularly IL-6, are involved in prostate cancer development. The discrepancy between the effect of the two prostate cancer cell lines on cytokine secretion by PBMC may be due to their different androgen dependency.

Caffeine alters cytokine secretion by PBMC induced by colon cancer cells.

BACKGROUND: Studies have shown that caffeine might be capable to prevent colon cancer development. This activity is linked in part to its anti-inflammatory properties mediated through modulation of immune responses. It was the aim of the study to evaluate the role of caffeine in the immune balance between peripheral blood mononuclear cells (PBMC) and those of HT-29 and RKO human colon cancer lines. METHODS: Cytokine production was evaluated following incubation of the two types of cancer cells without and with three concentrations of caffeine. RESULTS: A concentration-dependent inhibition of TNFα and IFNγ secretion by PBMC was observed only after their stimulation by cancer cells. Reduction of the anti-inflammatory IL-1ra and IL-10 production was observed using higher caffeine concentrations only. CONCLUSION: We presume that by changing the equilibrium between pro- and anti-inflammatory cytokines in favor of anti-inflammation, caffeine may reduce the inflammatory process with a consequent suppression of colorectal cancer progress.

An alternative facility for a stroke unit in a community hospital.

OBJECTIVE: The administration of tissue plasminogen activator (tPA) to patients with acute ischemic stroke (AIS) within three hours from onset of neurological symptoms is presently accepted as the standard treatment for suitable individuals, since it has been shown that it improves their outcome. The aim of this retrospective study was to report our experience with tPA administration in a subunit of a department of internal medicine adapted specifically for that goal. SETTING: The study was carried out in a subunit of a department of internal medicine. This subunit was equipped with all necessary items for monitoring vital signs. The patients received 0.9mg/kg of tPA intravenously and remained under around-the-clock supervision by highly trained nurses. SUBJECTS: Thirty one patients (11 women and 20 men), diagnosed with AIS between 2004 and 2008, and eligible for tPA treatment, were included in the study. RESULTS: The interval from the onset of stroke to tPA administration (onset to treat time OTT) was 145±2.2min, whereas the interval from door-to-needle was 100±4min. Two patients (6.4%) died during hospitalization because of severe intracerebral hemorrhage. Three patients with hemiparesis (9.6%) developed minor hemorrhages detected by brain CT. The mean length of stay was 8.8±0.6days. CONCLUSIONS: Our results are comparable with those obtained in stroke units in other countries. The suggested model offers a possibility for appropriate and rapid thrombolysis for AIS in a community hospital lacking special stroke unit. Moreover, the suggested alternative does not require extensive economic investment, since there is no need for additional staff, and permits the use of already existing hospital facilities.

Statins as modulators of colon cancer cells induced cytokine secretion by human PBMC.

The study was designed to examine whether the hydrophilic statin - pravastatin and the hydrophobic statin - simvastatin affect colon cancer cell-induced cytokine secretion by peripheral blood mononuclear cells (PBMC). Statins were added to human colon cancer cells (HT-29 and RKO), or to PBMC incubated separately or jointly. The secretion of the pro-inflammatory cytokines IL-1ß and IFNγ and that of the anti-inflammatory cytokines IL-1ra and IL-10 induced by cancer cells was decreased by simvastatin but not by pravastatin, whereas that of IL-6 was not affected by both drugs. Conditioned media from colon cancer cells incubated with either simvastatin or pravastatin induced stimulation of cytokine production by PBMC similar to that caused by conditioned media derived from cancer cells incubated without the drugs, suggesting that simvastatin acts directly on the interaction between cancer and PBM cells. Simvastatin, but not pravastatin, caused inhibition of both cancer cell proliferation. The results imply that simvastatin may affect inflammation-induced colon cancer proliferation via alteration of the equilibrium between pro- and anti-inflammatory cytokines.

Nephrolithiasis: evaluation and management.

Nephrolithiasis is a major cause of morbidity involving the urinary tract. The prevalence of this disease in the United States has increased from 3.8% in the 1970s to 5.2% in the 1990s. There were nearly two million physician-office visits for nephrolithiasis in the year 2000, with estimated annual costs totaling $2 billion. New information has become available on the clinical presentation, epidemiologic risk factors, evaluative approach, and outcome of various therapeutic strategies. In this report, we will review the epidemiology and mechanisms of kidney-stone formation and outline management aimed at preventing recurrences. Improved awareness and education in both the general population and among health-care providers about these modifiable risk factors has the potential to improve general health and decrease morbidity and mortality secondary to renal-stone disease.

Inflammation and colorectal cancer: does aspirin affect the interaction between cancer and immune cells?

The effect of aspirin on colon-cancer-cell-induced cytokine secretion by peripheral blood mononuclear cells (PBMC) was examined. Aspirin was added to human colon cancer cells (HT-29 and RKO) or to PBMC incubated separately or jointly. The secretion of IFNγ, IL-6, and IL-10 induced by HT-29 cells was decreased, that of IL-1ß was slightly increased, whereas IL-1ra production was not affected. With RKO cells, aspirin reduced IL-6, IL-1ra, and IL-10 synthesis and enhanced IFNγ secretion, while IL-1ß remained unchanged. Conditioned media from colon cancer cells incubated without or with aspirin stimulated cytokine productions by PBMC similarly, suggesting that aspirin acts on the cell-to-cell interaction between cancer cells and PBMC. The results indicate that aspirin alter the balance between pro- and anti-inflammatory cytokines generated by interaction between colon cancer and immune cells disclosing an additional role of the drug in affecting inflammation-induced colon cancer.

Popeye domain-containing 1 is down-regulated in failing human hearts.

Congestive heart failure, a complex disease of heterogeneous etiology, involves alterations in the expression of multiple genes. The Popeye domain-containing (POPDC) family of three novel muscle-restricted genes (POPDC1-3) is evolutionarily conserved and developmentally regulated. In mice, POPDC1 has been shown to play an important role in skeletal and cardiac muscles subjected to injury or stress. However, it has never been explored in human hearts. In biopsies from non-failing and failing human hearts, we examined the cellular distribution of POPDC1 as well as the expression patterns of POPDC1-3 mRNAs. POPDC1 was visualized by immunohistochemistry and estimated by Western immunoblotting. The mRNA levels of POPDC1-3 and ß myosin heavy chain (MYHC7) were assessed using reverse transcription/quantitative polymerase chain reaction. POPDC1 was predominantly localized in the sarcolemma with an enhanced expression in the intercalated discs. In failing hearts, many cardiomyocytes appeared deformed and POPDC1 labeling was deranged. The three POPDC mRNAs were expressed in the four heart chambers with higher transcript levels in the ventricles compared to the atria. Heart failure concurred with reduced levels of POPDC1 mRNA and protein in the left ventricle. Correlation analyses of mRNA levels among the failing heart specimens indicated the coordinated regulation of POPDC1 with POPDC3 and of POPDC2 with MYHC7. It can be concluded that POPDC gene expression is modified in end-stage heart failure in humans in a manner suggesting regulatory and/or functional differences between the three family members and that POPDC1 is particularly susceptible to this condition.

On the combined effect of statins and lycopene on cytokine production by human peripheral blood cells.

Since both statins and lycopene exert immunomodulatory activities following incubation with human peripheral blood mononuclear cells (PBMC), the present work was designed to examine whether they may induce a synergistic or antagonistic effect on cytokine production while applied together. Peripheral blood mononuclear cells isolated from 15 healthy subjects were incubated for 24 h as follows: (1) without and with 0.125 or 0.25 microM lycopene, (2) without and with 10 or 50 mM pravastatin or simvastatin, and (3) with lycopene and with one of the statins together at the respective doses. The production of the following cytokines was assessed: interleukin (IL)-1beta, IL-1ra, IL-2, and IL-10, as well as tumor necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma). The results showed that lycopene and simvastatin applied together reduced TNFalpha and IFNgamma secretion, and abolished the increased production of the proinflammatory cytokine IL-1gamma caused by incubation with simvastatin only, an observation suggesting that simultaneous administration of both substances may reduce inflammatory responses.

Coenzyme Q10 decreases TNF-alpha and IL-2 secretion by human peripheral blood mononuclear cells.

The beneficial effect of coenzyme Q10 (CoQ10) on human health occurs through various mechanisms including the possibility of immunomodulation. Therefore, the purpose of study was to examine the in vitro effect of CoQ10 on cytokine production and superoxide anion generation by human peripheral blood mononuclear cells (PBMC). 2x10(6)/mL PBMC obtained from 19 volunteers were incubated for 24 h without or with 0.6, 1.25, 2.5 and 5.0 muM of CoQ10. The production of the following cytokines were examined: IL-1beta, IL-1ra, IL-6, IL-10, IL-2 and IFNgamma. Superoxide anion production was examined by incubation of 4x10(6)/mL cells with CoQ10 and 2x10(-3) mM phorbol merystate acetate (PMA) for 60 min. The production of the proinflammatory cytokines IL-1beta, IL-6 and IFNgamma and that of the anti-inflammatory cytokines IL-1ra and IL-10 by PBMC was not affected by CoQ10, whereas TNFalpha secretion was significantly decreased when the cells were incubated with 0.6 and 1.25 muM of CoQ10. On the other hand, increasing doses of CoQ10 caused mild, but statistically significant inhibition of IL-2 secretion. The generation of superoxide anion by PBMC did not differ significantly between cells incubated with or without CoQ10 at concentrations between 0.3 and 5.0 muM. The results suggest that CoQ10 exerts a certain effect on cytokine production by PBMC related to its capacity to modulate human immune function.

Citrus pectin affects cytokine production by human peripheral blood mononuclear cells.

Dietary fibers, including pectin, have been shown to exert a favorable effect on a wide spectrum of pathological conditions. Their positive influence on human health is explained by their anti-oxidative, hypocholesterolemic and anti-cancerous effects. However, little has been reported about their activity on the immune system. Therefore, the present study was undertaken to examine the effect of citrus pectin (CP) on cytokine production by human peripheral blood cells (PBMC). PBMC were incubated without or with CP at different degrees of esterification (DE) (approximately 30, approximately 60 and approximately 90% esterified pectin, assigned as DE30, DE60 and DE90, respectively) for detection of IL-1 beta, IL-1 ra, TNFalpha, IL-6 and IL-10 secretion. Incubation with DE60 and DE90 induced a dose-dependent inhibition of the pro-inflammatory cytokine IL-1 beta secretion, whereas D30 did not affect this function. However, CP at all three esterification degrees did not alter the secretion of the additional pro-inflammatory cytokines examined, i.e. TNFalpha and IL-6. Conversely, CP at DE60 and DE90 caused a dose-dependent increased secretion of the anti-inflammatory cytokines IL-1 ra and IL-10, whereas D30 did not affect the production of IL-1 ra and decreased that of IL-10. The findings indicate that CP possesses the capacity to exert an immunomodulatory response in human PBMC which may have a favorable effect on human health.

In vitro effect of lycopene on cytokine production by human peripheral blood mononuclear cells.

There is evidence indicating that regular consumption of tomato products is associated with favorable immunomodulatory effects. In addition, tomato extracts have been shown to possess antioxidant, anticarcinogenic and antithrombotic activity in vitro. Since tomatoes are rich in carotenoids and particularly in lycopene--the pigment responsible for the red color of tomatoes--the present work was designed to examine the in vitro effect of lycopene on cytokine production by peripheral blood mononuclear cells (PBMC) from 15 healthy subjects. First, 2 x 10(6) PBMC suspended in 1 ml of conditioned medium were incubated over a period of 24 and 48 hours without or with the following concentrations of lycopene: 0.25, 0.5, 1.0, 2.0 and 4.0 microM. The production of the subsequent cytokines was evaluated: IL-1beta, IL-1ra, IL-2, IL-6 and IL-10, as well as TNFalpha and IFNgamma. Lycopene induced a dose-dependent increase in IL1beta, and TNFalpha production and a decrease in IL-2, IL-10 and IFNgamma secretion, whereas that of IL-6 and IL-1ra was not affected. It is concluded that understanding the role of lycopene in modulation of the immune system may promote decisions as for dietary supplementation of lycopene for reducing the risk of certain diseases.

Hydrophobic but not hydrophilic statins enhance phagocytosis and decrease apoptosis of human peripheral blood cells in vitro.

The engulfing ability of phagocyting cells is related to the fluidity of the cell membrane that in turn depends on its chemical composition. Changes in membranal lipid content may increase or decrease membranal fluidity with a subsequent enhanced or impaired phagocytosis, respectively. Statins are recognized as potent inhibitors of cholesterol synthesis and therefore, are successfully administered to patients with hypercholesterolemia. Since it is considered that cholesterol affects cell function via changes in membrane composition, the present study was designed to examine the in vitro effect of three hydrophobic statins--atorvastatin, lovastatin and simvastatin, and a hydrophilic one--pravastatin, on the engulfing capacity, phagocytic index and apoptosis of peripheral blood phagocytes from healthy volunteers. Peripheral white blood cells obtained from 20 healthy normocholesterolemic individuals were incubated for 2h with 10 and 50 microM of the four statins and phagocytosis of fluorescent latex particles was detected by flow cytometry. Apoptosis was examined using annexin V and propidium iodide staining. An increase in the percentage of phagocyting cells was observed after incubation with 50 microM of lovastatin and simvastatin. On the other hand, all three hydrophobic statins induced a dose-dependent increase in the phagocytic index. The hydrophilic pravastatin did not affect phagocytosis, phagocytic index and apoptosis. All three hydrophobic statins at 50 microM exerted a slight, but significant decrease of apoptosis. The results suggest that the effect of hydrophobic statins on the engulfing capacity of human peripheral blood phagocytes and apoptosis is dependent on their dosage and physiochemical properties. This observation is an additional contribution to the statins' pleiotropic effect.