Function Of Peripheral Blood Monocytes Research Articles

Monocyte dysfunction in decompensated cirrhosis is mediated by the prostaglandin E2-EP4 pathway

Background & AimsInfection is a major problem in advanced liver disease secondary to monocyte dysfunction. Elevated prostaglandin (PG)E2 is a mediator of monocyte dysfunction in cirrhosis; thus, we examined PGE2 signalling in outpatients with ascites and in patients hospitalised with acute decompensation to identify potential therapeutic targets aimed at improving monocyte dysfunction.MethodsUsing samples from 11 outpatients with ascites and 28 patients hospitalised with decompensated cirrhosis, we assayed plasma levels of PGE2 and lipopolysaccharide (LPS); performed quantitative real-time PCR on monocytes; and examined peripheral blood monocyte function. We performed western blotting and immunohistochemistry for PG biosynthetic machinery expression in liver tissue. Finally, we investigated the effect of PGE2 antagonists in whole blood using polychromatic flow cytometry and cytokine production.ResultsWe show that hepatic production of PGE2 via the cyclo-oxygenase 1–microsomal PGE synthase 1 pathway, and circulating monocytes contributes to increased plasma PGE2 in decompensated cirrhosis. Transjugular intrahepatic sampling did not reveal whether hepatic or monocytic production was larger. Blood monocyte numbers increased, whereas individual monocyte function decreased as patients progressed from outpatients with ascites to patients hospitalised with acute decompensation, as assessed by Human Leukocyte Antigen (HLA)–DR isotype expression and tumour necrosis factor alpha and IL6 production. PGE2 mediated this dysfunction via its EP4 receptor.ConclusionsPGE2 mediates monocyte dysfunction in decompensated cirrhosis via its EP4 receptor and dysfunction was worse in hospitalised patients compared with outpatients with ascites. Our study identifies a potential drug target and therapeutic opportunity in these outpatients with ascites to reverse this process to prevent infection and hospital admission.Lay summaryPatients with decompensated cirrhosis (jaundice, fluid build-up, confusion, and vomiting blood) have high infection rates that lead to high mortality rates. A white blood cell subset, monocytes, function poorly in these patients, which is a key factor underlying their sensitivity to infection. We show that monocyte dysfunction in decompensated cirrhosis is mediated by a lipid hormone in the blood, prostaglandin E2, which is present at elevated levels, via its EP4 pathway. This dysfunction worsens when patients are hospitalised with complications of cirrhosis compared with those in the outpatients setting, which supports the EP4 pathway as a potential therapeutic target for patients to prevent infection and hospitalisation.

Evaluation of Immunologic Function of Peripheral Blood Monocytes from Schizophrenic Patients in Response to Toxoplasma Gondii

Background: It has been suggested that the function of myeloid immune cells, especially macrophages in schizophrenia patients (SCZ), is impaired. Considering the role of macrophages in induction of inflammatory responses, the purpose of this study is to examine the response of monocyte-derived macrophages (MDM) of schizophrenia patients to Toxoplasma gondii (T. gondii) challenge. Materials and Methods: MDMs were generated from 20 SCZ and 10 healthy controls (HC). The cells were exposed to T. gondii. The Cytokine (IL-10, IL-12, IL-6, and TNF-α) and nitric oxide (NO) productions were measured. The expression of miR146a and miR155 was examined using qPCR. Results: The level of NO was significantly higher in the supernatant of MDMs of SCZ compared with the HC (P≤0.05) in response to T. gondii. There was no difference in cytokine (IL-10, IL-12, IL-6, and TNF-α) production of SCZ compared to the controls. The effect of miR-155/ miR-146a on inflammatory cytokine production was confirmed using anti-miRNAs. There were no significant effect in miR-155/ miR-146a expression of macrophages of schizophrenia patients to T. gondii compared to control. Conclusion: In this study, although the cytokine response and the amount of miR-155/ miR-146a expression of macrophages to T. gondii was not significantly different between the schizophrenia patients and the healthy subjects, the significant differences in the production of nitric oxide strengthen the hypothesis of the functional failure of these cells.

Effect of Yangxinshi tablets on the phenotype and function of monocytes in patients with unstable angina pectoris of coronary heart disease

Objective: The objective of this study was to observe the effect of Yangxinshi tablets on the phenotype and function of peripheral blood monocytes in patients with unstable angina of coronary heart disease (CHD) and to explore the possible mechanism of Yangxinshi tablets in the treatment of CHD. Methods: A total of 100 patients with unstable angina of CHD were randomly divided into two groups: Group A – treatment group and Group B – control group. The phenotypic and functional changes in blood monocytes and the changes in serum inflammatory factors before and after treatment were compared in the two groups. Results: The expression of CD14+CD163+ interleukin (IL)-10+ was significantly higher in the control group than in the patients with unstable angina of CHD, whereas the expression of CD14+CD163−IL-12+ was lower. The concentration of IL-10 was higher in the control group than in the patients with unstable angina, whereas the concentration of tumor necrosis factor-α (TNF-α) and IL-12 was significantly lower. In Group A, the expression of CD14+CD163+, CD14+CD206+, and CD14+CD163+CD206+ in peripheral blood monocytes increased after treatment than before treatment, whereas the expression of CD14+CD163−CD206− decreased. The expression of CD14+CD163−IL-12+ decreased after treatment than before, whereas CD14+CD163+IL-10+ expression increased. The serum concentration of IL-10 in Group A was higher after treatment than before, whereas that of IL-12 and TNF-α was lower. In Group B, the phenotype and function of the peripheral blood monocytes remained unchanged. Conclusion: Yangxinshi tablet therapy can change the phenotype of the peripheral blood monocytes in patients with unstable angina of CHD. Yangxinshi tablet therapy changes the inflammatory state in patients with an increase in the expression of anti-inflammatory factors and a decrease in the expression of inflammatory factors.

Alterations to the frequency and function of peripheral blood monocytes and associations with chronic disease in the advanced-age, frail elderly.

BackgroundCirculating myeloid cells are important mediators of the inflammatory response, acting as a major source of resident tissue antigen presenting cells and serum cytokines. They represent a number of distinct subpopulations whose functional capacity and relative concentrations are known to change with age. Little is known of these changes in the very old and physically frail, a rapidly increasing proportion of the North American population.DesignIn the following study the frequency and receptor expression of blood monocytes and dendritic cells (DCs) were characterized in a sample of advanced-age, frail elderly (81–100 yrs), and compared against that of adults (19–59 yrs), and community-dwelling seniors (61–76 yrs). Cytokine responses following TLR stimulation were also investigated, as well as associations between immunophenotyping parameters and chronic diseases.ResultsThe advanced-age, frail elderly had significantly fewer CD14(++) and CD14(+)CD16(+), but not CD14(++)CD16(+) monocytes, fewer plasmacytoid and myeloid DCs, and a lower frequency of monocytes expressing the chemokine receptors CCR2 and CX3CR1. At baseline and following stimulation with TLR-2 and -4 agonists, monocytes from the advanced-age, frail elderly produced more TNF than adults, although the overall induction was significantly lower. Finally, monocyte subset frequency and CX3CR1 expression was positively associated with dementia, while negatively associated with anemia and diabetes in the advanced-age, frail elderly.ConclusionsThese data demonstrate that blood monocyte frequency and phenotype are altered in the advanced-age, frail elderly and that these changes correlate with certain chronic diseases. Whether these changes contribute to or are caused by these conditions warrants further investigation.

Mesenchymal Stem Cells Inhibit Dendritic Cell Differentiation and Function by Preventing Entry Into the Cell Cycle

Mesenchymal stem cells (MSCs) play a crucial role in hematopoietic development and have been shown to exert a powerful immunosuppressive effect. In this study, we investigated the effect of bone marrow MSC on the differentiation and function of peripheral blood monocytes into dendritic cells (DCs). Human MSCs, generated from normal bone marrow, were added to peripheral blood monocytes stimulated in vitro with granulocyte-macrophage colony stimulating factor and interleukin-4 to become DCs. Monocytes were then examined for the expression of markers characteristic of DCs and their ability to stimulate allogeneic T cells. In addition, the effect of MSCs on the cell cycle of monocyte-derived DCs and the expression of various cell cycle proteins were analyzed by cytometric analysis and Western blotting with specific antibodies. MSCs blocked the differentiation of monocytes into DCs and impaired their antigen-presenting ability. This resulted from a block of monocytes from entering the G1 phase of the cell cycle with a progressive number of cells accumulating in the G0 phase. Cyclin D2 was downregulated. However, differently from what was observed in T-cells stimulated in the presence of MSCs, the expression of p27 was found decreased, suggesting the involvement of similar but not identical pathways. We conclude that MSCs impair monocyte differentiation and function by interfering with the cell cycle. These findings imply that MSC-induced immunosuppression might be a side product of a more general antiproliferative effect.

Administration of granulocyte colony-stimulating factor induces hyporesponsiveness to lipopolysaccharide and impairs antigen-presenting function of peripheral blood monocytes.

The incidence and severity of acute graft-vs-host disease after allogeneic transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) are not greater than those after conventional bone marrow transplantation despite infusion of more than one log greater number of donor T cells in PBSC. It has been postulated that monocytes from G-CSF-mobilized donors suppress alloreactivity of donor T cells. We investigated the phenotype and function of monocytes in normal individuals receiving 10 microg/kg of G-CSF for 4 days. Monocytes were phenotypically and functionally different after G-CSF administration from steady-state monocytes. They were characterized by an increased CD14(+)CD16(+) subpopulation, reduced expression of HLA-DR, and diminished ability to produce tumor necrosis factor-alpha and interleukin-10 to lipopolysaccharide, compared with steady-state monocytes. These alterations were not replicated by culturing monocytes with G-CSF in vitro, suggesting an indirect effect of G-CSF. In addition, the antigen-presenting function of G-CSF-mobilized monocytes was impaired. Hyporesponsiveness of G-CSF-treated monocytes to lipopolysaccharide with regard to tumor necrosis factor-alpha production, together with impaired antigen-presenting function, may be responsible for the unexpectedly low incidence of graft-vs-host disease after G-CSF-mobilized PBSC transplantation.

Phagocytic activity of monocytes in patients with breast cancer at different clinical stages

The investigation was designed to evaluate numerical and functional properties of peripheral blood monocytes (PBMo) in patients with breast cancer at different clinical stages. Monocyte phagocytosis test was performed in 19 patients with benign breast tumor, 29 patients with breast cancer and 10 healthy subjects. Cancer patients were divided into three groups on the basis of the clinical stage of disease: groupA, patients with localized disease; groupB, patients with regional lymph node metastasis; and groupC, patients with distant metastasis. Patients with advanced disease (groupC) showed an increase in neutrophils, but no differences in the total count of leukocytes and absolute number of lymphocytes as compared with healthy individuals, patients with benign breast tumor or patients with lower stage. However, the mean number of monocytes decreased in patients with benign disease and further decreased in cancer patients, reaching the significantly lowest value in patients with distant metastasis. Phagocytic activity of PBMo was found to be significantly lower in patients with benign tumor, and it became further reduced in the cancer group, related to the clinical stage. Thus, we noted a sixfold decrease in the capacity of phagocytosis, fourfold decrease in percentage of phagocytosis and twofold decrease in phagocytic index in patients with advanced stage (groupC). The alterations in number and function of PBMo in patients with benign and malignant breast tumor were observed in close association with clinical stage of disease, and thus they could be considered as indicators of tumor progression. However, further studies are required to determine whether monocyte dysfunction could provide additional prognostic information in the case of breast cancer diagnosis and therapy.

Monocyte phagocytic function in patients with breast cancer during therapy

The present study was designed to elucidate phagocytic function of peripheral blood monocytes in patients with breast cancer during surgery and chemotherapy. Absolute and relative number of peripheral blood leukocytes and monocyte phagocytic function (percentage of phagocytosis [PP], phagocytic index [PI] and capacity of phagocytosis [CP]) were determined in 29 patients with breast cancer and 10 healthy individuals. These parameters were determined at the time of diagnosis, following surgery and after chemotherapy. The total count of circulating leukocytes, and absolute and relative counts of polymorphonuclears and lymphocytes were not significantly different between investigated groups, before and after therapy. The mean number of monocytes was significantly lower in cancer patients at diagnosis, but increased following surgery reaching the control value. There were no significant postchemotherapy changes in the number of monocytes. PP, PI and CP were decreased at the time of diagnosis. PP and CP recovered to normal values following surgery, but PI remained decreased. Following chemotherapy PP and CP remained stable, whereas PI further decreased reaching the values significantly lower than those found before the start of chemotherapy. However, 3 months after last cycle of chemotherapy, all tested parameters returned to normal values. These results showed that phagocytic activity of cancer patients' monocytes, decreased at diagnosis, returned within the normal range after surgical therapy. However, we need time to determine whether the alteration in PBMo phagocytic activity may provide additional prognostic information when monitoring surgically treated breast cancer patients.

Role of increased production of monocytes TNF-α, IL-1β and IL-6 in psoriasis: relation to focal infection, disease activity and responses to treatments

To evaluate the immunological function of peripheral blood monocytes (PBMC) in psoriasis, we measured spontaneous production of the inflammatory cytokines, TNF-α, IL-1β and IL-6 from the PBMC of psoriasis patients, by enzyme linked immunosorbent assay (ELISA). The production of all three inflammatory cytokines by psoriatic PBMC was significantly higher than that by normal control PBMC. PBMC sampled from active psoriasis produced three cytokines significantly higher than samples from inactive psoriasis. In addition, IL-1β and TNF-α production showed a positive relation to clinical severity, but IL-6 did not. TNF-α production increased much more than did the others. Therefore, the TNF-α to IL-1β ratio was significantly higher, even in inactive psoriasis, than that of the normal control. In relation to focal infection, psoriatic PBMC sampled 3 h after a tonsillar provocation test increased cytokine production, compared with the level before provocation. The cases which responded to tonsillectomy or systemic methotrexate therapy, but not the non-responding cases, showed a significant decrease in PBMC cytokine productivity. These results strongly suggest that inflammatory cytokines, especially TNF-α, from monocytes are involved in the pathogenesis of psoriasis, and activated monocytes may work as an effective mediator of focal infection in skin lesions.

Monocyte function in cattle experimentally infected with bovine immunodeficiency-like virus

The effects of bovine immunodeficiency-like virus (BIV) on monocyte function were examined in experimentally infected cattle and in monocytes infected in vitro. Infection with the R29 isolate of BIV appeared to have relatively little effect on monocyte function in cattle during the first 2 years postinfection (PI). For the first 4 to 8 months post infection, monocyte phagocytosis of Staphylococcus aureus tended to be lower ( P=0.06) in BIV infected calves than in control animals. After 8 months PI, however, phagocytosis became equal between the two groups. Random and chemotactic migration and antibody-dependent cell-mediated cytotoxicity (ADCC) did not appear to be affected by BIV infection. Monocytes from BIV infected cattle were able to respond to in vitro treatment with interferon γ similarly to monocytes from control cattle. Although experimental infection with BIV R29 resulted in minimal effects on monocyte function, this result could have been due either to a low virus burden in vivo or because BIV is intrinsically unable to affect monocyte function. To distinguish between these possibilities, monocytes from control, uninfected cattle were treated with BIV virus in vitro. Treatment of normal monocytes with cell-free virus significantly ( P<0.05) increased phagocytosis and random and chemotactic migration and decreased ADCC, in a dose-dependent manner. It appears, therefore, that the normal function of peripheral blood monocytes in the BIV R29 infected animals may be due to a low virus burden rather than to the inability of BIV to affect monocyte function. The in vitro infection results also raise the possibility that the function of monocyte derived cells at local sites of BIV replication may be altered.

T Cell Lymphokine-Induced Secretion of Cytokines by Monocytes from Patients with Multiple Sclerosis

To investigate the function of peripheral blood monocytes in multiple sclerosis (MS), we measured the production of the cytokines interleukin-1β (IL-1β), tumor necrosis factor α (TNFα), and interleukin-6 (IL-6), and the procoagulant, tissue factor (TF) in 17 patients with chronic progressive MS and 15 normal controls. Monocyte activity was tested under unstimulated, minimal endotoxin conditions and after culture with various stimuli, including Escherichia coli lipopolysaccharide (LPS), crude supernatant from anti-CD3-activated T cells, recombinant interleukin-2 (rIL-2), and recombinant interferon-γ (rIFN-γ). A higher number of MS patients than controls had circulating monocytes which spontaneously secreted IL-6 or contained detectable cell-associated IL-1β. Monocyte responses to LPS were comparable between the two groups: LPS caused production and secretion of all cytokines and TF in every MS patient and control. In contrast crude T cell supernatants, rIL-2, and rIFN-γ induced IL-1β release in a higher number of MS monocytes than that in controls, whereas the production and secretion of the other cytokines and TF activity were similar between the groups. We conclude that some MS patients have "primed" circulating monocytes, as shown by excessive spontaneous IL-6 release and intracellular IL-1β synthesis. Unstimulated MS monocytes, however, are not different from controls with respect to spontaneous secretion of small amounts of IL-1β and TNFα and expression of cell surface TF. Excessive IL-1β secretion by MS monocytes after stimulation with T-cell-derived lymphokines suggests dys-regulation of T cell-monocyte interactions which may be most relevant in the central nervous system plaques where activated T cells are found.

Angiogenic Activity is Defective in Monocytes from Patients with Alopecia Universalis

Monocyte/macrophages are important components of cell-mediated immune responses in presentation of antigen, as regulators of lymphocyte function, and as sources of cytokines that modulate functions of cells other than those of the immune system. Their role in the pathogenesis of alopecia areata (AA) and universalis (AU) has not been explored. This study is an investigation of the function of peripheral blood monocytes from normal subjects and patients with AA, AU, and alopecia totalis (AT), with respect to the principal macrophage-derived angiogenic factor, tumor necrosis factor alpha (TNF alpha). Because neovascularization is a necessary component in the anagen phase of hair growth and may play a role in the pathology of these disorders, we asked whether monocyte/macrophage angiogenic activity was compromised in these alopecias. Purified preparations of monocytes were activated in culture. Conditioned media were assessed for angiogenic activity on the chick chorioallantoic membrane and for concentration of TNF alpha by enzyme-linked immunosorbent assay (ELISA). Both angiogenic and the TNF concentration were significantly diminished in conditioned media from AU monocytes when compared to those from normal subjects and patients with AA. These results show that the function of AU monocytes may be abnormal and that the abnormality may distinguish AU from AA. Defective monocyte/macrophage function could also play a pathogenic role via effects on neovascularization and/or modulation of the immune response.

HIV-1 and its envelope glycoprotein down-regulate chemotactic ligand receptors and chemotactic function of peripheral blood monocytes.

Peripheral blood monocytes from AIDS patients exhibit defective migratory responses to chemotactic stimuli in vitro and to inflammatory sites in vivo. In studies presented here, normal monocytes were infected with the HIV-1/HTLV-IIIBa-L isolate in vitro and evaluated for chemotactic responsiveness. Within 2 days after viral exposure, but before evidence of virus production in the monocytes, chemotactic activity was significantly impaired. Decreased chemotactic activity was associated with modulation of receptors for the chemotactic ligands, C5a and FMLP, on the monocyte cell surface. In addition to HIV-1, monocytes treated with purified HIV-1 envelope glycoprotein gp120 demonstrated a comparable modulation of chemotactic ligand receptors and migratory function. In addition, the HIV-1 or HIV-1 gp120-treated monocytes were induced to undergo differentiation as monitored by HLA-DR expression. Immunoprecipitation of the gp120 with a specific antibody reversed its effects on monocyte chemotaxis and HLA-DR expression. Taken together, these data indicate that the initial interaction of HIV-1 with the monocyte is not passive, but that the binding of HIV-1 and/or HIV-1 gp120 to the CD4R on monocytes transduces a signal leading to transient monocyte activation.

Recombinant Human Granulocyte/Macrophage Colony-Stimulating Factor Enhances Monocyte Cytotoxicity and Secretion of Tumor Necrosis Factor a and Interferon in Cancer Patients

The colony-stimulating factors (CSFs) promote the proliferation and differentiation of hematopoietic precursors and more recently have been shown to amplify the functions of mature phagocytes in vitro. In this study recombinant human granulocyte/macrophage colony-stimulating factor (rGM-CSF) was administered to cancer patients to determine whether the cytotoxic and secretory activity of their blood monocytes could be enhanced. Patients with refractory neoplastic disease were treated with rGM-CSF either as a single bolus or as a constant infusion for 14 days at either 100 or 500 micrograms/m2 per day. As has been reported by others, the number of peripheral blood monocytes and granulocytes rose markedly in a dose-response fashion during infusion with rGM-CSF. The functional capacity of monocytes was increased by rGM-CSF, since the cytotoxicity of monocytes against antibody-coated xenogeneic cells was increased during the constant infusion compared to baseline. In addition, monocytes harvested during the constant infusion and stimulated with lipopolysaccharide (LPS) in vitro secreted increased quantities of tumor necrosis factor alpha (TNF-alpha) and interferon (IFN). These data indicate that rGM-CSF can enhance both the number and the function of peripheral blood monocytes in vivo.

Recombinant human granulocyte/macrophage colony-stimulating factor enhances monocyte cytotoxicity and secretion of tumor necrosis factor alpha and interferon in cancer patients

The colony-stimulating factors (CSFs) promote the proliferation and differentiation of hematopoietic precursors and more recently have been shown to amplify the functions of mature phagocytes in vitro. In this study recombinant human granulocyte/macrophage colony-stimulating factor (rGM-CSF) was administered to cancer patients to determine whether the cytotoxic and secretory activity of their blood monocytes could be enhanced. Patients with refractory neoplastic disease were treated with rGM-CSF either as a single bolus or as a constant infusion for 14 days at either 100 or 500 micrograms/m2 per day. As has been reported by others, the number of peripheral blood monocytes and granulocytes rose markedly in a dose-response fashion during infusion with rGM-CSF. The functional capacity of monocytes was increased by rGM- CSF, since the cytotoxicity of monocytes against antibody-coated xenogeneic cells was increased during the constant infusion compared to baseline. In addition, monocytes harvested during the constant infusion and stimulated with lipopolysaccharide (LPS) in vitro secreted increased quantities of tumor necrosis factor alpha (TNF-alpha) and interferon (IFN). These data indicate that rGM-CSF can enhance both the number and the function of peripheral blood monocytes in vivo.

In vitro and in vivo activation of human mononuclear phagocytes by interferon-gamma. Studies with normal and AIDS monocytes.

To determine the potential immunotherapeutic role of interferon-gamma (IFN-gamma) as a mononuclear phagocyte-activating agent, we examined the effector cell function of peripheral blood monocytes from healthy donors and acquired immunodeficiency syndrome (AIDS) patients after either in vitro and/or in vivo treatment with recombinant (r) IFN-gamma. When assayed immediately after a 24-hr in vitro pulse with 300 U/ml, normal and AIDS monocytes behaved similarly with little augmentation of their intrinsically high levels of H2O2 release and activity against Toxoplasma gondii; in contrast, activity toward the more resistant intracellular pathogen, Leishmania donovani, was appreciably enhanced by rIFN-gamma. In addition, upon testing 4 to 6 days after in vitro pulsing, both normal and AIDS monocytes showed clear evidence of persistent activation in all three assays. The capacity of IFN-gamma to similarly activate monocytes in vivo was confirmed in all ten treated AIDS patients by examining cells before and after 24-hr infusions of 0.03 and 0.5 mg of rIFN-gamma/square meter (M2) of body surface area. For postinfusion monocytes tested after 1 day in culture, H2O2 release and antitoxoplasma activity were essentially unchanged, but antileishmanial effects were augmented. After 5 to 7 days in culture, monocytes from treated patients showed 3.2- to 5.9-fold increases in H2O2-releasing capacity and increases of 49 to 68% and 35 to 61% in intracellular activity against T. gondii and L. donovani, respectively. These results indicate that the human monocyte can be induced by rIFN-gamma to express signs of both immediate and persistent activation and suggest that, as a direct activator of mononuclear phagocytes, rIFN-gamma may also have potential as an immunotherapeutic agent for patients with intracellular infections.

Monocyte dysfunction in human cancer.

General immunobiologic studies in cancer patients have stressed measurements of lymphocyte function and have commonly ignored the monocyte-macrophage system. A preliminary study of peripheral blood monocyte-macrophage function was undertaken in a group of 90 cancer patients (18 breast, 32 colon, 13 head and neck, 9 lung, and 18 melanoma) and 70 controls. Studies included enumeration of extractible monocytes (EM), quantitation of differentiation into macrophages (macrophage precursor test: MP), evaluation of antibody-dependent cellular cytotoxicity (ADCC), and spontaneous cellular cytotoxicity (SCC) as measured with human erythrocytes, and measurements of monocyte and serum lysozyme activity. Breast cancer patients had normal profiles. Colon cancer patients showed the most profound abnormalities with decreased EM and MP and increased ADCC and SCC. Patients with Stage I and Stage II melanoma had normal profiles, whereas those with advanced melanoma had significantly decreased MP. This defect was restored in two patients by BCG immunotherapy. Head and neck cancer and benign breast disease patients had decreased EM, whereas patients with lung cancer had increased EM. Monocyte lysozyme production was unchanged in the cancer patients compared to controls. Serum lysozyme levels, however, were significantly increased in patients with cancers of the colon, head and neck, and lung. Although patients with localized breast cancer and melanoma had normal levels, these were increased in both patient groups with advanced disease. It would appear that the source of the increased serum lysozyme is probably not the peripheral blood monocytes, but could have originated in the intra-tumoral or tissue-bound macrophages which were not examined. Selected assays of peripheral blood monocyte function were deranged in certain types of cancer patients but were fully normal in others, and did not show consistent correlations with tumor type or stage. Tissue-bound or intra-tumoral macrophages might provide a more fruitful area for study in these disease categories.

Defective function of peripheral blood monocytes in patients with Hodgkin's and non-Hodgkin's lymphomas.

Phagocytosis and lysis of C. pseudotropicalis by peripheral blood monocytes from Hodgkin's and non-Hodgkin's lymphoma were analysed. In Hodgkin's disease, there was a decrease in the phagocytic activity of blood monocytes; moreover, the candidacidal activity was significantly decreased as compared with normal controls. Although monocytes from non-Hodgkin's patients presented normal phagocytic function, the ability to kill C. pseudotropicalis was impaired. In both groups of lymphomas, the data showed that the abnormal findings were not related to treatment. These results indicate that monocytes from Hodgkin's and non-Hodgkin's lymphoma posses a deficiency in killing C. pseudotropicalis, which could be due to an intrinsic macrophage defect in the myeloperoxidase-independent mechanisms and which may be responsible for the predisposition of the se patients to candida infections.

Macrophage precursors in ovarian carcinoma

Monocyte differentiation into macrophage was measured in 21 patients with ovarian carcinoma and 34 normal age-matched controls as a test of peripheral blood monocyte function. Monocyte to macrophage maturation in vitro was significantly decreased in patients with Stage III ovarian carcinoma. Studies using normal cells with normal sera in criss-cross investigations with cancer patients' cells and cancer patients' sera suggest that both a cellular defect and a serum factor are involved. Administration of intradermal Corynebacterum parvum to a volunteer induced increased monocyte maturation.

Irradiation and monocyte function in patients with breast cancer

We have measured peripheral blood monocyte function in breast cancer patients, using a maturation assay and a colony-forming assay. The results indicate that the changes in these two functions induced by local radiotherapy, are inversely related, so that patients showing an increase in circulating colony forming cells have monocytes with a decreased maturation index.