Enhancement of CD3AK cell proliferation and killing ability by α-Thujone.

Thujone is a monoterpene ketone natural substance found mainly in wormwood and sage. Previous studies have shown that Thujone has various pharmacological effects, such as anti-tumor, analgesic, and insecticide. The effect of α-Thujone to human immune cells is still unknown. Our study focuses on investigating the effects and mechanism of α-Thujone to CD3AK (anti- CD3 antibody induced activated killer) cells proliferation and cytotoxicity to colon cancer cell lines. With cell proliferation and FCM assay, it is found that α-Thujone could significantly enhance CD3AK cell proliferation and expression of CD107a in a dose-dependent manner. The cytotoxicity to colon cancer cells detected by CCK-8 assay is also improved. The expressions of TNF-α and FasL detected with ELISA assay were not significantly changed. Mechanically, the study shows that α-Thujone could enhance the expression of p-ERK1/2 and p-Akt. In addition, α-Thujone has no cytotoxicity to HCT116 and SW620 cells proliferation. In a word, α-Thujone enhances CD3AK cell proliferation and cytotoxicity via the improvement of expression of CD107a, p-Akt and p-ERK1/2.

Near eradication of clinically relevant concentrations of human tumor cells by interferon-activated monocytes in vitro.

We have previously reported that low concentrations of interferon (IFN)-activated monocytes exert near-eradicative cytocidal activity against low concentrations of several human tumor cells in vitro. In the present study, we examined 7 human tumor cell lines and 3 diploid lines in the presence or absence of 10 ng/mL IFNα2a and monocytes. The results confirmed strong cytocidal activity against 4 of 7 tumor lines but none against 3 diploid lines. To model larger in vivo tumors, we increased the target cell concentration and determined the concentration of IFNα2a and monocytes, required for cell death. We found that increasing the tumor cell concentration from 10- to 100-fold (10(5) cells/well) required an increase in the concentration of IFNs by over 100-fold and monocytes by 10-fold. High concentrations of monocytes could sometimes kill tumor or diploid cells in the absence of IFN. We may conclude that killing of high concentrations of tumor or diploid cells required high concentrations of monocytes that could sometimes kill in the absence of IFN. Thus, high concentrations of tumor cells required high concentrations of IFN and monocytes to cause near eradication of tumor cells. These findings may have clinical implications.

Photochemotherapy induces the apoptosis of monocytes without impairing their function.

BACKGROUND: Extracorporeal photopheresis (ECP) is a powerful therapy currently used to treat various hematological disorders as in graft versus host disease. Clinical data clearly demonstrate its efficacy and immunomodulation toward the pathogenic T cells. However, ECP mechanism of action is still poorly understood. Monocytes represent up to 30% of the total amount of treated cells and are known to play an important role in adaptive immunity. However, data from previous reports analyzing the effect of psoralen and UV-A irradiation (PUVA) on their functions are heterogeneous. In this study, we focused on the effect of PUVA on human monocytes functions in adaptive immunity. DESIGN AND METHODS: Purified human monocytes were treated in vitro by PUVA. We measured their kinetic of apoptosis after the treatment. We also determine whether their phenotype and functionalities were modified. Finally, we assessed the functionalities of PUVA-treated monocytes-derived dendritic cells (DC). RESULTS: PUVA treatment sentenced purified monocytes to die in 6 days and immediately altered their migratory capacities without impairing their ability of endocytosis. It also up-regulated co-stimulatory molecules and production of inflammatory cytokines on activation and consequently stimulated allogeneic or autologous T cells as efficiently as untreated monocytes. Moreover, PUVA-treated monocytes retained their ability to differentiate into fully functional DC that maturated and stimulated T cells as well as normal DC. CONCLUSIONS: Our data demonstrate that monocytes undergo apoptosis and loose a part of their migratory capacity after ECP and the surviving cell functionalities are not impaired, suggesting that monocytes have a minor effect on ECP-mediated immunomodulation.

CVT-E002 stimulates the immune system and extends the life span of mice bearing a tumor of viral origin.

The present study evaluated the dose-related effects of CVT-E002, a proprietary extract of Panax quinquefolius (CV Technologies Inc., Edmonton, AB), in the treatment of a tumor of viral origin, that is, erythroleukemia, in mice. Three treatments including ingestion of 2, 40, and 120 mg/d were compared. The study revealed that the dose of 40 mg/d was particularly effective in stimulating cells mediating nonspecific immunity and extending the life span of tumor-bearing mice. This study represents the first in vivo demonstration of the anticancer efficacy of CVT-E002 in an animal model. CVT-E002 treatment significantly elevated the absolute numbers of natural killer cells and monocytes and reduced the number of tumor cells in the bone marrow and spleen. This study has shown that (1) approximately 30 to 50% of tumor-bearing mice administered CVT-E002 at a dose of 40 mg/d achieved a significantly extended life span, and (2) dosage is critical in producing these ameliorative effects.

Leukotriene B4 activates T cells that inhibit B-cell proliferation in EBV-infected cord blood-derived mononuclear cell cultures.

Epstein-Barr virus (EBV)-specific cellular memory is not transferred from mother to child. Therefore, EBV-induced B-cell proliferation in in vitro-infected cord blood mononuclear cell cultures is not inhibited. However, by addition of immunomodulators, polysaccharide K (PSK) or truncated thioredoxin (Trx80) that activate monocytes, EBV-specific T-cell response could be generated in such cultures. Presently, we demonstrate that leukotriene B(4) (LTB(4)) is involved in the effect of the immunomodulators. LTB(4) was detected in the medium, and T-cell activation was compromised by addition of leukotriene biosynthesis inhibitors. Moreover, we found that LTB(4) added to infected cultures, which did not receive the immunomodulators, induced functional activation of the T cells. LTB(4) activated the monocytes and acted directly on the T cells. In consequence, addition of LTB(4) inhibited the EBV-induced proliferation of B lymphocytes. Specific cytotoxicity could be generated by restimulation of the T cells. The experiments showed successive stages of T-cell activation in acquisition of their immunologic effector function. This is orchestrated by complex cellular interactions, and autocrine loops mediated by soluble factors-here interferon (IFN)-gamma, interleukin (IL)-15, IL-12, and LTB(4). Importantly, the results indicate that endogenous LTB(4) can induce T-cell activation that inhibits the EBV-induced proliferation of B lymphocytes.

Glucocorticosteroid therapy decreases CD14-expression and CD14-mediated LPS-binding and activation of monocytes in patients suffering from systemic lupus erythematosus.

In order to study the possible action of glucocorticosteroids (GCS) on the CD14/Toll like receptor mediated activation of monocytes the CD14-expression, CD14-mediated LPS binding and activation of these cells of patients suffering from Systemic Lupus Erythematosus receiving no, low dose or pulse steroid treatment was studied. The CD14-expression was determined on whole blood monocytes by flow cytometry, while the LPS-binding of an FITC-LPS preparate and the LPS-induced TNFalpha secretion were tested on isolated monocytes. The CD14-dependent and -independent LPS-binding and activation were evaluated with the help of a blocking anti-CD14 mAb. Our results showed that the CD14-expression, CD14-dependent LPS-binding and activation were significantly inhibited by the in vivo applied pulse steroid therapy. In contrast, the CD14-independent LPS-binding and activation were not altered by the GCS treatment. Our data provide further in vivo evidence for a possible new way of GCS therapy is able to initiate its anti-inflammatory action.

Augmented 18F-FDG uptake in activated monocytes occurs during the priming process and involves tyrosine kinases and protein kinase C.

UNLABELLED: Activated monocytes with a high (18)F-FDG accumulation can affect the results of clinical PET studies. To better understand the mechanisms regulating monocytic (18)F-FDG uptake, we investigated the effect of priming and respiratory-burst generation and further evaluated the role of potential protein kinase pathways. METHODS: Purified human monocytes were primed with interferon-gamma (IFN-gamma), and respiratory burst was generated by stimulation of primed cells with phorbol-12-myristate-13-acetate (PMA). Oxygen-intermediate generation was assessed by luminescence measurements after the addition of lucigenin. (18)F-FDG uptake after 30 min of incubation was measured for unprimed control cells, primed cells, and PMA-stimulated cells. The role of protein kinases was investigated using respective inhibitors. RESULTS: PMA stimulation of primed monocytes dramatically increased oxygen-intermediate generation, leading to a 42.2 +/- 1.1 fold higher level of cumulative luminescence compared with unprimed control cells, whereas IFN-gamma priming alone resulted in low luminescence levels (13.9% +/- 4.6% of PMA-stimulated cells). In contrast, priming alone was sufficient to augment monocytic (18)F-FDG uptake to 273.3% +/- 16.7% of control levels (P < 0.001), and it was not further increased by PMA stimulation. The tyrosine kinase inhibitor, genistein, and the specific protein kinase C inhibitor, staurosporine, completely abolished the priming-induced enhancement of (18)F-FDG uptake and lowered uptake to control levels. Under the same conditions, wortmannin, a phosphatidylinositol 3 kinase (PI3 kinase)-specific inhibitor, and cycloheximide, a protein synthesis inhibitor, were associated with only minor reductions in the enhanced-uptake effect of priming. CONCLUSION: IFN-gamma priming alone, without stimulation of respiratory-burst activity, is sufficient to induce maximal augmentation of (18)F-FDG uptake in monocytes. Furthermore, this metabolic effect appears to involve tyrosine kinases and the protein kinase C pathway but is independent of the PI3 kinase pathway.

Role of Paracoccidioides brasiliensis cell wall fraction containing beta-glucan in tumor necrosis factor-alpha production by human monocytes: correlation with fungicidal activity.

The polysaccharide fraction of Paracoccidioides brasiliensis mycelial cell wall (F1 fraction), the active component of which is composed of beta-glucan, was investigated in regard to the activation of human monocytes for fungal killing. The cells were primed with interferon-gamma (IFN-gamma) or F1 (100 and 200 microg ml(-1)) or F1 (100 and 200 microg ml(-1)) plus IFN-gamma for 24 h and then evaluated for H2O2 release. In other experiments, the cells were pretreated with the same stimuli, challenged with a virulent strain of P. brasiliensis and evaluated for fungicidal activity and levels of tumor necrosis factor (TNF-alpha) in the supernatants. F1 increased the levels of H2O2 in a similar manner to IFN-gamma. However, a synergistic effect between these two activators was not detected. On the contrary, a significant fungicidal activity was only obtained after priming with IFN-gamma plus F1. This higher activity was associated with high levels of TNF-alpha in the supernatants of the cocultures. Overall, P. brasiliensis F1 fraction induced human monocytes to release relatively high levels of TNF-alpha, which, in combination with IFN-gamma, is responsible for the activation of human monocytes for effective killing of P. brasiliensis.

[Large-capacity expanded cytoline-induced killer cells and its cytotoxic activity].

This study was conducted to establish the large-capacity culture methd of cytokine-induced killer (CIK) cells for clinical therapy and assess its effect on the fuction of cell-mediated immunity following autologous CIK cells reinfusion. Autologus CIK cells were expanded in 1000 ml culture-bag and reinfused back. The MTT method was used to test the cytotoxic activity of CIK cells before and after reinfusion. The results showed that the total amount of autologous CIK cells reinfusion exceeded 1.6 x 10(10) with the use of the culture method of large-capacity. The PBMNC from patients treated by CIK cells showed significant increase in cytotoxic activity, no side effects were observed, and therefore the large-capacity culture method of CIK cells is a simle and safe therapy for treating the minimum residue of diseases.

Toxicity of human THP-1 monocytic cells towards neuron-like cells is reduced by non-steroidal anti-inflammatory drugs (NSAIDs).

There is mounting evidence that inflammatory processes, including activation of microglia, are upregulated in Alzheimer's disease. The importance of this phenomenon is indicated by multiple epidemiological studies showing that patients taking non-steroidal anti-inflammatory drugs (NSAIDs) have a substantially reduced prevalence of Alzheimer's disease. The pharmacological actions of anti-inflammatory drugs in brain are still uncertain. As a step towards identifying key pharmacological targets, we developed a neurotoxicity assay based on the property of supernatant media from stimulated human monocytic THP-1 cells to cause human neuroblastoma cell death. Similar neurotoxicity was observed when postmortem human microglia were substituted for THP-1 cells, establishing the validity of the assay for simulating neurotoxicity in human brain. A combination of lipopolysaccharide and interferon-gamma was used to activate the THP-1 cells. NSAIDs were effective in inhibiting neurotoxicity by this assay, while steroidal anti-inflammatories and propentofylline had no effect. The neuroprotective potency of NSAIDs appeared to be unrelated to their selective ability to inhibit cyclooxygenase-1 (COX-1) or cyclooxygenase-2 (COX-2). It is suggested that inhibition of monocyte cytotoxicity might be responsible for the apparent beneficial effects of NSAIDs in Alzheimer's disease.

Apoptotic cell death in activated monocytes following incorporation of clodronate-liposomes.

The present study was performed to elucidate whether sterically stabilized liposomes laden with clodronate, which lead to depletion of macrophages (Mphis) and amelioration of experimental autoimmune arthritis in vivo, selectively affect cells of the mphi lineage in vitro. The rates of incorporation of drug-free, fluorescent liposomes and the rates of cell death following exposure to clodronate-liposomes were assessed in human peripheral blood monocytes, as well as in polymorphonuclear leukocytes (PMNs), T cells, endothelial cells, and fibroblasts, both at rest and following activation. Gel electrophoresis of nuclear extracts and ultrastructural analyses were performed to identify the modality of cell death. Monocytes, particularly upon activation, were more efficient in incorporating sterically stabilized liposomes than all other cells except PMNs. Twenty percent of resting monocytes and up to 65% of activated monocytes died within 24 h of exposure to clodronate-liposomes, whereas the other cell types, including PMNs, remained unaffected. Activated monocytes exposed to clodronate-liposomes, but not resting or activated monocytes exposed to drug-free liposomes, showed clear signs of apoptotic cell death. In most of the assays, sterically stabilized liposomes were more efficient than conventional phosphatidylcholine-liposomes. Sterically stabilized clodronate-liposomes preferentially affect cells of the mphi lineage, particularly if activated. Selective elimination of activated Mphis by apoptosis may explain both therapeutic efficacy and safety of clodronate-liposomes in experimental models of autoimmunity.

Synthetic macrophage activating peptides derived from the N-terminus of human MCF.

Recently, we described the purification and N-terminal sequencing of a novel cytokine termed MCF (Monocyte Cytotoxicity Inducing Factor) (1,2). In order to study the interaction of this cytokine with monocytes, we synthesized a nona-peptide GAAVLEDSQ corresponding to the N-terminus of MCF: two truncated peptides, GAAVL and LEDSQ; and the substituted peptide, GAAVLENSQ. The authentic N-terminal peptide is biologically active in the nanomolar range, while substitution of asparagine for aspartic acid at position 7 diminishes biological activity. Biological activity was observed from the C-terminal fragment LEDSQ, but the N-terminal pentapeptide (GAAVL) was devoid of biological activity. Scatchard analysis revealed a single class of saturable high affinity sites. These studies indicate that the N-terminus of MCF is important in interacting with the binding site on monocytes and it may be possible to design synthetic activators and inhibitors of monocyte/macrophage cytotoxicity.

Lymphotoxin lacks effects on 75-kDa receptors in cytotoxicity on U-937 cells.

We examined differences in cytotoxic activity between human lymphotoxin (LT) and tumor necrosis factor (TNF) as functions of their interaction with two types of TNF receptors, 55-kDa (p55R) and 75-kDa (p75R). Cytotoxic activity of LT was much lower than that of TNF on a human monocytic cell line, U-937, on which p75R was predominant. Monoclonal antibodies specific for p55R (htr-5 and htr-9) and p75R (utr-1) significantly diminished TNF cytotoxicity, whereas, utr-1 was only slightly inhibitory to LT cytotoxicity, and htr-5 reduced it significantly. TNF individual binding to p75R increased cytotoxic activity when p55R was occupied by htr-9 and a mutein of TNF which significantly lost affinity to p75R. However, LT binding to p75R did not increase. Scatchard analysis with [125I]LT and [125I]TNF showed that LT still had approximately half of the affinity to p75R and slightly less affinity to p55R than TNF. These results indicate slight cytotoxicity of LT compared to TNF, due to inability of LT to signal through p75R on U-937 cells without significant loss of affinity to p75R.

Dysfunctional monocytes from a patient with disseminated Mycobacterium kansasii infection are activated in vitro and in vivo by GM-CSF.

A 27 year-old woman presented with disseminated infection due to Mycobacterium kansasii. Signs and symptoms of disseminated infection persisted despite the administration of multiple antimycobacterial agents to which her organism was sensitive for 15 months. She was seronegative for HIV-1 and functional studies of T and B lymphocytes and granulocytes failed to demonstrate any abnormality. Peripheral blood monocytes proved abnormally permissive to the intracellular growth of Mycobacterium avium and M. kansasii, and expressed normal number of receptors to interferon-gamma, but reduced numbers of receptors to granulocyte monocyte colony stimulating factor and tumor necrosis factor. These defects were partially reversed with in vitro exposure of her cells to recombinant GM-CSF. In addition, administration of recombinant human GM-CSF in vivo (250 mg/M2 per day) for 10 days armed her circulating monocytes as evidenced by increased production of O2- in response to phorbol esther and, when infected ex vivo with M. kansasii, enhanced inhibition of intracellular growth compared with pre-therapy monocytes. These defects reappeared with discontinuation of GM-CSF and resolved with its re-administration. While a salutary clinical and microbiologic effect was difficult to assess, administration of GM-CSF in vivo was associated with in vitro activation of monocytes and enhanced mycobactericidal activity in this patient with a defect in monocyte function.

Effect of ibuprofen on monocyte activation by liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (CGP 19835A): can ibuprofen reduce fever and chills without compromising immune stimulation?

The purpose of this study was to determine the effects of ibuprofen on the ability of liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) to activate human blood monocytes in vitro. We undertook these experiments because the major toxic side-effects following L-MTP-PE infusion, fever and chills, could be prevented when ibuprofen was given orally immediately before L-MTP-PE infusion. It was therefore important to determine whether ibuprofen interfered with the macrophage-activation properties of L-MTP-PE. Peripheral blood monocytes were isolated from normal donors, then incubated with L-MTP-PE in the presence or absence of ibuprofen. The cytotoxic properties of the monocytes were assessed by a radioisotope-release assay against A375 cells. Ibuprofen at dose levels of 40 micrograms/ml suppressed the generation of the cytotoxic phenotype but did not interfere with the killing process once the cells were activated. Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) production, as well as the mRNA expression of these cytokines, was suppressed by 40 micrograms/ml ibuprofen. Since IL-1 and TNF play a crucial role in the cytotoxic function of monocytes, these findings may explain the mechanism by which ibuprofen inhibited the generation of the cytotoxic phenotype by L-MTP-PE. By contrast, ibuprofen dose levels up to 10 micrograms/ml had no effect on the generation of monocyte-mediated cytotoxicity by L-MTP-PE and no effect on the production, secretion, or mRNA expression of TNF and IL-1. Therefore, we concluded that if ibuprofen is to be used to control the side-effects of L-MTP-PE, blood levels of up to 10 micrograms/ml are desirable. In two of three patients, we determined that an oral dose of 200 mg given immediately before L-MTP-PE infusion could achieve these desired blood levels.

Phase II study of liposomal muramyl tripeptide in osteosarcoma: the cytokine cascade and monocyte activation following administration.

PURPOSE: A phase II trial that uses liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) in patients with relapsed osteosarcoma is underway. To determine if in vivo cytokine induction plays a role in the mechanism of action of L-MTP-PE, we investigated the circulating cytokine levels of 16 patients who were undergoing therapy. PATIENTS AND METHODS: Patients had histologically proven osteosarcoma and pulmonary metastases that developed either during adjuvant chemotherapy or that were present at diagnosis and persisted despite chemotherapy. Patients were rendered disease-free by surgery. The major goal of the study was to improve the disease-free interval in this high-risk group. L-MTP-PE 2 mg/m2 was infused during a 1-hour period twice a week for 12 weeks, then once a week for 12 weeks. Serial blood samples were collected after L-MTP-PE administration and were assayed for cytokine levels (tumor necrosis factor-alpha [TNF alpha] interleukin-1 alpha [IL-1 alpha], IL-1 beta, IL-6, interferon-gamma [IFN-gamma], neopterin, C-reactive protein). RESULTS: After the infusion of L-MTP-PE, there was rapid induction of circulating TNF alpha and IL-6. TNF alpha levels peaked 1 to 2 hours after infusion in 10 of 16 patients, whereas peak IL-6 levels were detected at 2 to 3 hours in all patients. Induction of circulating TNF alpha and IL-6 was evident only after the first dose of L-MTP-PE. Neither IL-1 alpha nor IL-1 beta was detected in the plasma. Neopterin levels increased at 24 hours postinfusion, which indicated macrophage activation, and were not related to the induction of circulating IFN-gamma. C-reactive protein was elevated in all patients at 24 hours and decreased by 72 hours. Unlike circulating TNF alpha and IL-6, elevations in C-reactive protein and neopterin could be detected throughout the treatment course. CONCLUSION: It is concluded that L-MTP-PE has specific biologic effects in patients with osteosarcoma that may be important to the drug's immunostimulatory capacity and its effectiveness as an antitumor agent.

Frozen-thawed human blood monocytes respond reproducibly to activation stimuli: implications for screening of BRMs.

The purpose of this study was to identify the optimal freezing conditions for human blood monocytes to allow their recovery and use for in vitro screening of activation stimuli. Human monocytes separated from buffy coats of healthy blood donors were suspended at a density of 1 x 10(7) cells/ml in freezing medium consisting of 70% medium: 20% fetal bovine serum: 10% DMSO frozen in a stepdown freezer, and stored at -180 degrees C. Monocytes were thawed at different times up to 4 months later. Viability was > 90%. Fresh monocytes from different donors and frozen monocytes thawed at different times were incubated with different concentrations of lipopolysaccharide, muramyl tripeptide, muramyl dipeptide, or lipopeptide. Tumoricidal activity and IL-1 production of fresh monocytes varied greatly among the 5 different preparations. In contrast, the frozen monocytes (thawed at different times) produced uniform levels of antitumor activity and IL-1 production. These results show that monocytes recovered from frozen storage maintain their ability to respond to activation stimuli in a uniform and reproducible manner. Thus, the use of frozen-thawed monocytes is recommended for screening of macrophage-activating agents.

Lactoferrin inhibits or promotes Legionella pneumophila intracellular multiplication in nonactivated and interferon gamma-activated human monocytes depending upon its degree of iron saturation. Iron-lactoferrin and nonphysiologic iron chelates reverse monocyte activation against Legionella pneumophila.

We have been exploring the role of iron in the pathogenesis of the intracellular bacterial pathogen Legionella pneumophila. In previous studies, we have demonstrated that L. pneumophila intracellular multiplication in human monocytes is iron dependent and that IFN gamma-activated monocytes inhibit L. pneumophila intracellular multiplication by limiting the availability of iron. In this study, we have investigated the effect on L. pneumophila intracellular multiplication of lactoferrin, an iron-binding protein which is internalized via specific receptors on monocytes, and of nonphysiologic iron chelates which enter monocytes by a receptor-independent route. Apolactoferrin completely inhibited L. pneumophila multiplication in nonactivated monocytes, and enhanced the capacity of IFN gamma-activated monocytes to inhibit L. pneumophila intracellular multiplication. In contrast, iron-saturated lactoferrin had no effect on the already rapid rate of L. pneumophila multiplication in nonactivated monocytes. Moreover, it reversed the capacity of activated monocytes to inhibit L. pneumophila intracellular multiplication, demonstrating that L. pneumophila can utilize iron from the lactoferrin-lactoferrin receptor pathway. The capacity of iron-lactoferrin to reverse monocyte activation was dependent upon its percent iron saturation and not just its total iron content. Similarly, the nonphysiologic iron chelates ferric nitrilotriacetate and ferric ammonium citrate completely reverse and ferric pyrophosphate partially reversed the capacity of IFN gamma-activated monocytes to inhibit L. pneumophila intracellular multiplication, demonstrating that L. pneumophila can utilize iron derived from nonphysiologic iron chelates internalized by monocytes independently of the transferrin and lactoferrin endocytic pathways. This study suggests that at sites of inflammation, lactoferrin may inhibit or promote L. pneumophila intracellular multiplication in mononuclear phagocytes depending upon its degree of iron saturation. In addition, this study suggests a potential role for PMN in host defense against L. pneumophila--providing apolactoferrin to infected monocytes--and it supports the concept that PMN and monocytes may cooperate in host defense against intracellular parasites and other pathogens.

[Changes in the profile of cytotoxic mediator monocytes in patients with cancer and precancerous conditions of the stomach]. / Izmenenie profilia tsitotoksicheskikh mediatorov monotsitov u bol'nykh rakom i predrakovymi sostoianiiami zheludka.

Peripheral blood monocytes from healthy subjects, patients with gastric precancer disease (chronic gastric ulcer, stomach polyps and chronic atrophic gastritis) and different stages of gastric cancer were used. Spontaneous and lipopolysaccharide (LPS)-stimulated TNF-like factors production by monocytes was significantly higher in the precancer gastric disease patients than in the healthy subjects. At the same time the spontaneous capacity of monocytes to produce NTF-like factors was 2.5 lower in the gastric cancer patients compared to the healthy subjects. Moreover, in 5/13 of the gastric cancer patients in TNF-like factors production by the LPS-stimulated and non-stimulated monocytes was 1 unit/ml less. Spontaneous and reactive CL indexes were higher in the cancer patients monocytes than in the healthy subjects. The obtained results suggest that reactive oxygen species production can be an alternative mechanism by which a cytotoxic action of monocytes is regulated.