Cytokine Release Ensuing Interaction Between Human Peripheral Blood Mononuclears and Epstein-Barr Virus Transformed B-CLL Cell Line.

Introduction: B-cell chronic lymphocytic leukemia (B-CLL) is a common form of leukemia affecting mostly elderly individuals. The course of the disease is usually unremarkable, but because it may proceed with impaired immune defense, B-CLL might be complicated with infections and even death. The leukemic microenvironment containing a number of immune cells, mainly lymphocytes and macrophages capable to produce various molecules including inflammatory cytokines, plays an important role in the development and outcome of the disease. We studied the capacity of Epstein-Barr virus (EBV)-transformed B-cell chronic lymphocytic leukemia (B-CLL) cell line (EHEB) cells, an EBV-transformed line established from a B-CLL patient, to affect the production of inflammatory cytokines by human peripheral blood mononuclear cells (PBMC). Methods: PBMC isolated from peripheral blood of healthy donors were incubated either with EHEB cells or with their supernatants and the production of the following cytokines: tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, interferon (IFN)-γ, IL-1ra, and IL-10 were detected using the enzyme-linked immunosorbent assay method. Results: Direct contact of PBMC incubated with EHEB cells induced a marked increase of TNFα, IL-1ß, IL-6, IFNγ, and IL-10 release by the immune cells. Yet, incubation of PBMC with EHEB cells' supernatant resulted in a mild production of the same cytokines. Conclusions: The noticeable increased production of inflammatory cytokines by PBMC following direct contact with EHEB cells and to a lesser degree with their supernatants implies the existence of an immune dialogue between these two types of cells. The results support the concept that not only leukemic cells, but also peripheral blood mononuclears could serve as a therapeutic target for B-CLL.

The impact of three commercial sweeteners on cytokine expression by mononuclears impelled by colon carcinoma cells.

The study was designed to examine the immunomodulatory effect of three commercial sweeteners on human peripheral blood mononuclear cells (PBMC) and on the immune dialogue between these and human HT-29 and HuCC colon cancer lines. PBMC were incubated with Sweet'N Low, Splenda and Stevia and the cytokine production was examined. The cytokine release of PBMC co-cultured with colon cancer cells in the presence of sweeteners was evaluated. Sweet'N Low enhanced IFNγ, IL-1ß and IL-6 release, and augmented HuCC-induced IL-10 secretion. Splenda reduced IFNγ and TNFα secretion by LPS and HuCC stimulated PBMC and enhanced HuCC-induced IL-10 and IL-1ra production. Stevia reduced IL-1ß, TNFα and IL-1ra secretion prompted by HuCC and HT-29 cells and enhanced IL-6 production induced by HuCC. The inhibition of pro-inflammatory- and increased anti-inflammatory cytokines release by Splenda and Stevia indicate that they possess valuable potential as carcinopreventive agents.

Broccoli and human health: immunomodulatory effect of sulforaphane in a model of colon cancer.

The favourable properties of broccoli on human health are due to their abundant content of vitamins, minerals and isothiocyanates, the sulforaphane (SFN) being the most important. SFN is created from its precursor glucoraphanin and it is released by myrosinase enzymes produced during crushing of the plant. SFN has been shown to possess anti-inflammatory and anticancer properties. The aim of the study was to determine if SFN may affect the immune dialogue between human peripheral blood mononuclear cells (PBMCs) and HT-29 and RKO human colon cancer cells lines. Non- or mitogen-stimulated PBMCs were incubated with various concentrations of SFN, and the secretion of TNFα, IL-1ß, IL-6, IFNγ, IL-2, IL-10 and IL-1ra was determined. In addition, the effect of SFN on the production of these cytokines by PBMCs co-cultured with colon carcinoma cells was examined. SFN exerted a concentration-dependent inhibitory effect on the inflammatory cytokine production by the immune cells. The impact of SFN on the interaction between immune and colon cancer cells underscores its capacity for cancer prevention and development.

Probiotic strains modulate cytokine production and the immune interplay between human peripheral blood mononucear cells and colon cancer cells.

Human health is tightly connected with a great number of gut microbial cells designated as microbiome or microbiota. We have examined the effect of six microbial strains (MS) included in a commercial probiotic on cytokine production by human peripheral blood mononuclear cells (PBMC) and on their immune dialog with colon carcinoma cells. Non-stimulated and lipopolysaccharide (LPS)-stimulated PBMC were incubated for 24 h with MS. The secretion of tumor necrosis factor alpha (TNFα), IL-1ß, IL-6, interferon gamma, IL-10 and IL-1ra and the effect of MS on the immune interplay between PBMC and cells from HT-29 and RKO colon carcinoma lines were evaluated. MS incubated with non-stimulated PBMC induced high expression of all cytokines examined, whereas in those stimulated by LPS, variability in the results was observed. MS added to PBMC co-cultivated with HT-29 or RKO colon cancer cells resulted in downregulation of most cytokines except IL-6 and TNFα, and enhanced production of TNFα and IL-1ß. The MS incorporated in the probiotic affected PBMC' cytokine production and altered the cross-talk between immune and colon cancer cells. The results may clarify the way by which probiotics modify the intestinal environment resulting in a decline of colon cancer development.

Cytokine Production by Mononuclear Cells from Patients with Familial Infantile Bilateral Striatal Necrosis.

Prompted by findings suggesting immune instability in infantile bilateral striatal necrosis (IBSN), we evaluated levels of proinflammatory (tumor necrosis factor α, interleukin [IL]-1ß, IL-6, interferon [IFN]γ) and anti-inflammatory (IL-10 and IL-1ra) cytokines produced by peripheral blood mononuclear cells (PBMC) from 6 children with IBSN and 11 age-matched controls. Compared to controls, non-stimulated PBMC from the IBSN group produced a significantly lower level of IL-1ra (by 38%; p < 0.001) and significantly lower levels of TNFα, IL-1ß, and IFNγ (by 36% [p < 0.001], 25% [p = 0.06], and 32% [p < 0.02]) under PBMC stimulation. The severe cachexia manifesting shortly after IBSN onset may impair the immunological state, placing patients at risk of death from hyperpyrexia and sepsis.

Capsaicin Modulates the Immune Cross Talk Between Human Mononuclears and Cells from Two Colon Carcinoma Lines.

BACKGROUND: Capsaicin, the pungent alkaloid of the chili peppers, has gained a worldwide reputation. In addition to its culinary assets, capsaicin possesses analgesic, anti-inflammatory, antimicrobial, and even carcinopreventive properties. Considering the linkage between chronic inflammation and tumorigenesis, the aim of the study was to evaluate the role of capsaicin in the immune interplay between human peripheral blood mononuclear cells (PBMCs) and HT-29 or RKO cells from human colon carcinoma lines. METHODS: PBMCs were incubated for 24 hours with either HT-29 or RKO cells and concentrations of capsaicin ranging between 10 and 200 µM. Subsequently, the generation of the following cytokines was examined: tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, interferon (IFN)-γ, IL-1ra, and IL-10. RESULTS: Capsaicin caused a concentration-dependent inhibition of colon cancer cells proliferation but had no effect on PBMC viability. 200 µM of capsaicin suppressed the production of all cytokines tested. At lower concentrations, the secretion of TNF-α, IL-1ß, IFN-γ, IL-10, and IL-1ra was inhibited concentration-dependently, whereas that of IL-6 was stimulated. CONCLUSIONS: Capsaicin causes a concentration-dependent alteration of the immune balance between PBMC and colon carcinoma cells expressed as an inhibited generation of inflammatory cytokines. These findings indicate the existence of an additional immunomodulatory mechanism by which this alkaloid may prevent tumor development.

High temperature affects the phagocytic activity of human peripheral blood mononuclear cells.

BACKGROUND: The ability for engulfment of pathogens and inert particles is the key hallmark of the phagocytic cells. Phagocytes play a significant role in the modulation of local or extended inflammation. Since fever activates a number of factors linked with the immune response it was the goal of this study to examine the in vitro effect of hyperthermia on the phagocytic capacity, the number of phagocytic cells and the viability of human peripheral blood mononuclear cells (PBMC) at 37 and 40°C. METHODS: PBMC were incubated with 0.8 µm polysterene latex beads, for 2 hours at 37 and 40°C. The number of phagocytic cells, and that of latex particles internalized by each individual cell was counted with a light microscope. In addition, the percentage of viable cells and the number of active metabolic cells was evaluated. RESULTS: A temperature of 40°C significantly increased the number of phagocytic cells and the phagocytic index by 41 and 37% respectively, as compared to cells incubated at 37°C. While the number of vital cells (trypan blue test) did not differ statistically at both temperatures, the number of active metabolic cells (XTT test) after 2 h of incubation at 40°C was 17% higher as compared with that at 37°C. However, the number of active metabolic cells after 24 h of incubation at 40°C was 51% lower compared with cells incubated at 37°C. CONCLUSIONS: The increased phagocytic capacity of human peripheral blood monocytes at high temperature further enlightens the immunomodulatory effect of fever in the immune responses during inflammation.

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.

Mononuclear cells phagocytic activity affects the crosstalk between immune and cancer cells.

The "professional phagocytes", i.e. monocytes and macrophages, play an important role as eliminators of pathogens and as essential components of the immune system. It is well established that monocytes induced for phagocytosis by various stimulators, produce cytokines that are closely related to inflammation. Considering the role of inflammation in carcinogenesis and the existence of an immune dialog between mononuclear and cancer cells, the aim of the present work was to examine cytokine production by immune cells stimulated for phagocytosis by latex particles and incubated with cells from HT-29 and RKO human cancer lines. Human peripheral blood mononuclear cells (PBMC) were incubated with various numbers of polysterene latex beads, 0.8µm in diameter and the secretion of the following cytokines: TNF-α, IL-1ß and IL-6, IL-10 and IL-1ra was examined before and after further incubation with cells of the both cancer lines. Phagocytosis of latex beads by PBMC caused an increased production of TNF-α, IL-1ß and IL-10, whereas that of IL-6 declined. PBMC activated by latex beads and co-cultured with cancer cells generated lesser amount of the three pro-inflammatory cytokines TNF-α, IL-1ß and IL-6, while that of the anti-inflammatory IL-10 and IL-1ra remained unchanged. The results indicate that phagocytosis of polystyrene latex beads by human PBMC alters the dialogue between immune and cells of human colon carcinoma lines, an observation that may clarify the role of the immune cells in attenuating inflammation and restraining carcinogenesis.

Modulators affecting the immune dialogue between human immune and colon cancer cells.

The link between chronic inflammation and colorectal cancer has been well established. The events proceeding along tumorigenesis are complicated and involve cells activated at the cancer microenvironment, tumor infiltrating polymorphonuclears, immune cells including lymphocyte subtypes and peripheral blood mononuclear cells (PBMC), as well as tumor-associated macrophages. The immune cells generate inflammatory cytokines, several of them playing a crucial role in tumorigenesis. Additional factors, such as gene expression regulated by cytokines, assembling of tumor growth- and transforming factors, accelerated angiogenesis, delayed apoptosis, contribute all to initiation, development and migration of tumor cells. Oxygen radical species originating from the inflammatory area promote cell mutation and cancer proliferation. Tumor cells may over-express pro-inflammatory mediators that in turn activate immune cells for inflammatory cytokines production. Consequently, an immune dialogue emerges between immune and cancer cells orchestrated through a number of activated molecular pathways. Cytokines, encompassing migration inhibitory factor, transforming growth factor beta 1, tumor necrosis factor-α, Interleukin (IL)-6, IL-10, IL-12, IL-17, IL-23 have been reported to be involved in human cancer development. Some cytokines, namely IL-5, IL-6, IL-10, IL-22 and growth factors promote tumor development and metastasis, and inhibit apoptosis via activation of signal transducer activator transcription-3 transcription factor. Colon cancer environment comprises mesenchymal, endothelial and immune cells. Assessment of the interaction between components in the tumor environment and malignant cells requires a reconsideration of a few topics elucidating the role of chronic inflammation in carcinogenesis, the function of the immune cells expressed by inflammatory cytokine production, the immunomodulation of cancer cells and the existence of a cross-talk between immune and malignant cells leading to a balance in cytokine production. It is conceivable that the prevalence of anti-inflammatory cytokine production by PBMC in the affected colonic mucosa will contribute to the delay, or even to halt down malignant expansion. Targeting the interplay between immune and cancer cells by mediators capable to alter cytokine secretion toward increased anti-inflammatory cytokine release by PBMC and tumor associated macrophages, may serve as an additional strategy for treatment of malignant diseases. This review will focus on the inflammatory events preceding tumorigenesis in general, and on a number of modulators capable to affect colon cancer cell-induced production of inflammatory cytokines by PBMC through alteration of the immune cross-talk between PBMC and cancer cells.

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.

Role of peripheral blood mononuclear cells in the predisposition of obese individuals to inflammation and infection.

OBJECTIVE: To compare the production of pro- and anti-inflammatory cytokines by peripheral blood mononuclear cells (PBMC) from obese but otherwise healthy individuals to that of normal-weight volunteers. METHODS: 25 healthy normal-weight subjects and 41 obese individuals were enrolled. Weight and height were measured twice. PBMC were examined for their capacity to generate pro-inflammatory (TNF-α, IFN-γ, IL-1ß, IL-6, IL-2) and anti-inflammatory IL-10 and IL-1ra) cytokines. RESULTS: PBMC from obese individuals, compared to those from subjects with normal weight showed an increased production of the pro-inflammatory cytokines IL-2 (6.7 ± 0.4. vs. 4.9 ± 0.3 ng/ml; p = 0.003), TNF-α (505 ± 45 vs. 277 ± 32 pg/ml; p = 0.001), and IFN-γ (93.8 ± 6.0 vs. 73.9 ± 2.7 ng/ml; p = 0.0016). However, PBMC from obese individuals produced a lower amount of the anti-inflammatory cytokine IL-10 (651 ±72 pg/ml) versus those from subjects with normal weight (951 ± 133 pg/ml; p = 0.039). CONCLUSIONS: The findings imply that obese individuals are in a 'low-grade inflammatory state', presumed to be connected with metabolic and cardiovascular co morbidities. The surplus of pro-inflammatory cytokines produced by circulating mononuclear cells of obese individuals, together with those secreted by adipocytes and non-fat cells in the adipose tissue, may contribute to the predisposition of obese patients to inflammation and infections.

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.

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.

1α,25-Dihydroxyvitamin D3 modulates the interaction between immune and colon cancer cells.

Following observations indicating the existence of a relationship between immune and cancer cells in the course of tumor development, it was the aim of the study to establish the role of 1α,25-dihydroxyvitamin D3 (vit. D) in the functional equilibrium between cells from two human colon carcinoma lines-induced cytokine production by peripheral blood mononuclear cells (PBMC). PBMC were incubated with HT-29 and RKO human colon cancer cells with and without vit. D at final concentrations of 10⁻8, 10⁻7 or 10⁻6 M. The production of the cytokines TNF-α, IL-6 and IL-10, as well as the effect of the vitamin on tumor cell proliferation were evaluated. Incubation of PBMC with either HT-29 or RKO cells caused a significant stimulation of both pro- and anti-inflammatory cytokine generation. Addition of vit. D to the incubation mixture containing PBMC and cells of both colon carcinoma lines caused a marked inhibition of the generation of the pro-inflammatory cytokines TNF-α and IL-6 and to a lesser extent-of the IL-10. Vit. D did not affect the proliferation of the cancer cells. The results indicate the existence of a functional "dialog" between immune and cancer cells expressed by an alteration of their capacity for cytokine production and support the role of inflammation in carcinogenesis. The ability of vit. D to attenuate production of the pro-inflammatory cytokines when added to the incubation mixture containing PBMC and cancer cells endorses observations as for the beneficial role of the vitamin in suppressing inflammation with subsequent colon cancer prevention.

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.

Effect of early versus conventional epidural analgesia during labor on cytokine production.

OBJECTIVE: To compare the effect of early epidural analgesia (EEA) vs. conventional epidural analgesia (CEA) on cytokine production in mother and neonate. METHODS: Healthy parturients with uncomplicated term pregnancies were randomized into two groups: EEA - parturients who would receive epidural analgesia before onset of pain and the control group, CEA - parturients who would receive epidural analgesia after onset of pain. Cytokines were measured in maternal blood at randomization Visual Analog Scale (VAS) < 30], 24 h postpartum, and in cord blood. RESULTS: Forty-one women were studied. Epidural was performed in EEA when VAS was 23 ± 10 and in CEA when VAS was77 ± 10 (p < 0.0001). Background data were similar except for ruptured membranes at admission (EEA 15%, CEA 46.6%; p = 0.03), transient hypotension (EEA 20%, CEA 0%; p = 0.03), and meconium (EEA 25%, CEA 0%; p = 0.01). No significant differences were found in cytokine levels between groups at any time. Interleukin (IL)-6 levels changed significantly only in the control group (p = 0.046). There was significant correlation between baseline maternal IL-6 level and cord blood level in CEA (r = 0.59, p = 0.005), while no significant correlation existed in EEA (r = 0.33, p = 0.16). CONCLUSION: Although there was no significant difference in cytokine levels between the groups, EEA prevented the significant increase in IL-6 during labor and interrupted IL-6 fetal-maternal 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.

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.

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.