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M Alvarez-Mon

Publications and source records attributed to M Alvarez-Mon.

120 records · Page 7Linked to original sources
PubMed1987

Diminished natural killer activity in pregnancy: modulation by interleukin 2 and interferon gamma.

We investigated the alterations of natural killer (NK) cells in pregnancy, which led to decreased killing from the first trimester to the puerperium. We show that this phenomenon cannot be ascribed to a defective number of NK cells since the amounts of HNK-1+, CD16+ (Leu 11), and CD11b+ (OKM1) cells were within normal ranges. Recombinant interleukin 2 (rIL-2) corrects the functional defect in a dose and time-dependent manner, without modification in the surface phenotype of the population. Analysis of the pattern of target cell susceptibility to lysis, together with the similar ability of recombinant interferon gamma (rIFN-gamma) to correct the deficiency, and CD16+, CD3- phenotype of the precursor and effector lymphocytes, demonstrated that the induced cytotoxicity was mediated by NK cells. Inhibitors in pregnancy sera block IL-2 production by specific T cells, but we show that they do not influence either NK activity or its reconstitution by rIL-2. These findings place the deficiency at the level of NK cell maturation into cytotoxic effector lymphocytes. Thus, homeostasis of the NK activity of pregnant women may provide a biological model for clarifying the internal mechanisms regulating NK-cell activation in vivo. Present studies in vitro suggest that modulation of lymphokine production may play a role in the adaptive response of NK cells in pregnancy.

Cell Differentiation↗
PubMed1987

Clinical signification of natural killer activity in B-cell chronic lymphocytic leukemia.

The natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) and lymphocytes with the capacity to form stable rosettes with neuraminidase-treated sheep red blood cells (E+) was studied in 28 previously untreated patients (11 at stage 0, 10 at stage I and 7 at stages II and III, according to Rai's classification) and 7 treated patients with B-cell chronic lymphocytic leukemia (B-CLL), all of them at stage 0 according to Rai's classification after treatment, and in 15 healthy controls. The mean NK activities of PBMC and E+ lymphocytes from untreated patients were significantly decreased (p less than 0.001) when compared with those of PBMC and E+ lymphocytes, respectively, from healthy controls. However, PBMC and E+ cells from treated patients demonstrated NK activity similar to that of the corresponding cellular populations of controls (p greater than 0.05). Furthermore, there were no significant differences among the NK activities of E+ lymphocytes from untreated B-CLL patients in the different clinical stages 0, I, II and III, according to Rai's classification (p less than 0.05). These results demonstrate that the very low or undetectable levels of NK activity present in PBMC and E+ cell populations from previously untreated patients with B-CLL, regardless of the clinical stage of the disease, can be modified by systemic therapy with alkylating agents. Moreover, the NK activity of PBMC and E+ lymphocytes from some treated patients that have achieved the stage 0 according to Rai's classification after chemotherapy can be found within the range of the lytic activity shown by PBMC and E+ cells from normal donors.

Animals↗
PubMed1986

Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth.

This study examines the potential role of transforming growth factor beta (TGF-beta) in the regulation of human T lymphocyte proliferation, and proposes that TGF-beta is an important autoregulatory lymphokine that limits T lymphocyte clonal expansion, and that TGF-beta production by T lymphocytes is important in T cell interactions with other cell types. TGF-beta was shown to inhibit IL-2-dependent T cell proliferation. The addition of picograms amounts of TGF-beta to cultures of IL-2-stimulated human T lymphocytes suppressed DNA synthesis by 60-80%. A potential mechanism of this inhibition was found. TGF-beta inhibited IL-2-induced upregulation of the IL-2 and transferrin receptors. Specific high-affinity receptors for TGF-beta were found both on resting and activated T cells. Cellular activation was shown to result in a five- to sixfold increase in the number of TGF-beta receptors on a per cell basis, without a change in the affinity of the receptor. Finally, the observations that activated T cells produce TGF-beta mRNA and that TGF-beta biologic activity is present in supernatants conditioned by activated T cells is strong evidence that T cells themselves are a source of TGF-beta. Resting T cells were found to have low to undetectable levels of TGF-beta mRNA, while PHA activation resulted in a rapid increase in TGF-beta mRNA levels (within 2 h). Both T4 and T8 lymphocytes were found to make mRNA for TGF-beta upon activation. Using both a soft agar assay and a competitive binding assay, TGF-beta biologic activity was found in supernatants conditioned by T cells; T cell activation resulted in a 10-50-fold increase in TGF-beta production. Thus, TGF-beta may be an important antigen-nonspecific regulator of human T cell proliferation, and important in T cell interaction with other cell types whose cellular functions are modulated by TGF-beta.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1985

A potential role for adrenocorticotropin in regulating human B lymphocyte functions.

Adrenocorticotropin (ACTH) was found to enhance the growth and differentiation of human B lymphocytes. By using highly purified preparations of human tonsillar B cells, the effects of ACTH on the growth and differentiation of in vitro activated B cells were examined. Optimal concentrations of ACTH were found to increase the proliferation of activated B cells by twofold to threefold when ACTH was present in culture with either a B cell growth factor or recombinant interleukin 2 (IL 2). ACTH had essentially no effects when added to cultures of activated B cells in the absence of the growth factor. Additionally, when ACTH was added in conjunction with an optimal concentration of either a B cell differentiation factor or IL 2 to cultures of activated B cells, the combination of ACTH and factor enhanced Ig secretion by twofold compared with the factor alone. In the absence of the differentiative signal, ACTH had minimal effects on Ig production. Only the first 24 amino acid fragments of ACTH were required to enhance B cell growth and differentiation when combined with the appropriate, more classical signals. Thus, ACTH may have a physiologic role in regulating human B cell function.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Diminished T lymphocyte proliferative response to polyclonal mitogens in acute brucellosis patients.

T lymphocytes from 21 untreated patients with acute brucellosis were tested for their proliferative response to polyclonal mitogens. The purified T lymphocytes from these patients showed a defective proliferative response to plant lectins and anti CD3 monoclonal antibodies with respect to the response observed in T lymphocytes from 21 healthy controls (p < 0.05). This defective proliferative response was not corrected by the exogenous addition of interleukin-2 or tumor necrosis factors alpha or beta to the culture medium. After antibiotic therapy, the proliferative response to the mitogens in T lymphocytes was found to be similar to that of the healthy controls (p > 0.05), and significantly higher than that found before treatment (p < 0.05). It was concluded that T lymphocytes from acute brucellosis patients have a defective proliferative response to membrane mitogenic signals, which disappears when the patients are cured after antibiotic treatment.

Acute Disease↗
PubMedDate not supplied

Modulation of PECAM-1 (CD31) expression in human endothelial cells: effect of IFNgamma and IL-10.

Intercellular contacts formed between endothelial cells (EC) permit the formation of a confluent monolayer and play a major role in the recruitment and the migration of leukocytes in the inflammatory response. It is currently accepted that cytokines are responsible for the signals involved in the induction of such endothelial alterations. The platelet EC adhesion molecule (PECAM-1), a specific component of EC junctions, is one of many molecules which participate in the regulation of EC interaction with blood components. Given that the regulatory mechanisms which affect the expression of this adhesion molecule are only partially understood, the aim of the present study was to compare the effects of two antagonistic inflammatory cytokines, interferon (IFN)-gamma and interleukin (IL)-10, on the expression of PECAM-1. Human umbilical vein EC grown to subconfluence were stimulated with IL-10 (10 ng/ml) and/or IFNgamma (100 U/ml) for 24 h. PECAM-1 expression was determined by FACScan and immunofluorescence. Morphological analysis of the cell cultures was performed by optical and scanning electron microscopy. In the presence of IL-10, no changes in cell growth and morphology or in the intensity of PECAM-1 expression were observed. However, when the cultures were treated with IFNgamma, the EC acquired a fibroblast-like appearance, growth was disorganized and PECAM-1 disappeared from cell junctions. The mean intensity expression and the percentage of EC expression of this antigen were analyzed by flow cytometry and significantly decreased after culture in the presence of IFNgamma. The simultaneous addition of IFNgamma and IL-10 to the EC cultures induced modifications similar to those observed in the presence of IFNgamma alone. Regulation of the expression of PECAM-1 with the subsequent functional implications seems to be dependent upon the IFNgamma signal and it is unaffected by IL-10. The different effects shown by IL-10 and IFNgamma on the expression of PECAM-1 in EC could reflect opposite regulatory actions of the inflammatory response induced by these cytokines.

Blotting, Western↗
PubMedDate not supplied

[Immunological and inflammatory pathogenesis of asthma: the predominance of ontogenic Th2 and its relation to developing immunological mechanisms during fetal and neonatal stages. Therapeutic implications].

From an immunopathogenic vantage point, asthma appears to be a complex allergic/inflammatory disorder involving mechanism in which the specific immunological response shifts toward Th2 responses instead of Th1 responses. As a consequence of this shift, the cytokines IL-4, IL-5, IL-10, IL-13, TNF-alpha and CSF-GM are produced. The actions of these cytokines explain the phenomena of eosinophilic infiltration and mastocytic degranulation that characterize allergic asthma. The authors propose that the process of deviation toward Th2 responses occurs in the fetal stage and is a result of maternal immunological remodeling processes characteristics of pregnancy. In this period, the mother's mechanisms of immune rejection (mediated by Th1 lymphocytes and their cytokines IFN-gamma and IL-2) are detained or slowed, leading to the predominance of the Th-2 circuit. This predisposes the child to the development of an allergic response to a chance encounter with allergens, viruses and/or bacteria and/or parasites that activate the Th2 circuit. Moreover, deficits in the function of the Th1 circuit explain the sensitivity of the newborn to infections by viruses and other intracellular pathogens. Knowledge of these immunopathogenic mechanisms suggests that the future treatment of asthma and other allergic diseases will be based on the use of immunomodulators capable of stimulating Th1 response, thus achieving a) a god state of resistance to infection, and b) reductions of the production of pro-inflammatory cytokines. The experimental results of IL-12 in human beings with AM3 (an inductor of IFN-gamma and IL-12) support the pathogenic hypothesis proposed and open new ways for the treatment of asthma and other allergic diseases.

Asthma↗
PubMedDate not supplied

An extract of the fern Polypodium leucotomos (Difur) modulates Th1/Th2 cytokines balance in vitro and appears to exhibit anti-angiogenic activities in vivo: pathogenic relationships and therapeutic implications.

In the present study we show the capacity of an extract of the fern Polypodium leucotomos (PLE) to partially inhibit the production of cytokines showing a Th1 pattern (IL-2, IFN-gamma and TNF-alpha) in human PHA-stimulated peripheral blood mononuclear cells. The percentage of inhibition was 24% for IL-2, 72% for INF-gamma and 53% for TNF-alpha. With regard to Th2 cytokines, the addition of PLE resulted in a significant increase (33%) in IL-10 production. Surprisingly, the production of the inflammatory cytokine IL-6 was completely abolished (100% inhibition) by PLE at all doses tested. In a second experiment in vivo we show that, the topical application of PLE to the skin of hairless albino mice (Skh-1) significantly diminished the mast cell infiltrate as well as the number of blood vessels triggered by chronic ultraviolet B (UVB) irradiation. These data show that PLE moderately inhibits the immunological Th1 responses, thus explaining the immunosuppressive as well as the anti-inflammatory and antioxidant activities reported in other studies carried out with PLE. The clear inhibitory effect on TFN-alpha and IL-6 production strongly suggest that this may be the mechanism by which PLE: (a) inhibits angiogenesis in vivo in the mouse model described here, and (b) prevents Langerhans' cells depletion caused by solar irradiation in humans. Taken together, these data suggest that PLE works through the induction of suppressive/anti-inflammatory cytokines such as IL-10 and/or TGF-beta which in turn appear to allow the partial deactivation of macrophages or other accessory cells. These features suggest that PLE could be useful in the treatment of autoaggressive/inflammatory conditions due to an exacerbation of Th1 responses.

Angiogenesis Inhibitors↗
PubMedDate not supplied

Cyclosporine A shows immunosuppressor activity on T lymphocytes from the peripheral blood and synovial fluid of patients with autoimmune arthritis.

OBJECTIVE: This work studies the effects of Cyclosporine A (CsA) upon the activation and proliferation of mononuclear cells (MNC) from the peripheral blood (PB) of patients with chronic autoimmune arthritis and from healthy controls, and from the synovial fluid (SF) of patients. METHODS: In vitro studies of activation, proliferation, mRNA expression and lymphokine production were carried out. RESULTS: We found in the PB and SF MNCs from patients with autoimmune arthritis that CsA inhibits the proliferative response, activation antigen expression, IL-2 mRNA expression and IL-2 production induced by polyclonal mitogens in a dose dependent manner. CONCLUSION: CsA blocks lymphocyte activation in PB and SF MNCs from patients with autoimmune arthritis.

Antigens↗
PubMedDate not supplied

Endocrine and immune response to injury after open and laparoscopic cholecystectomy.

BACKGROUND: There is clinical evidence that the surgical insult experienced by patients who undergo laparoscopic cholecystectomy (LC) differs significantly from that experienced by those undergoing open cholecystectomy (OC). LC is accompanied by less pain, better ventilatory function and almost total absence of secondary paralytic ileus. The aim of the present study was to investigate the endocrine and immune response to the injury induced by both types of surgery. To this end, the relationship between levels of hormones of the hypothalamus-hypophysis-adrenal axis (indicators of stress) and cytokine levels was analyzed. METHODS: Blood samples from subjects undergoing either OC (n = 14) or LC (n = 14) were obtained 24 h before surgery and 24 h and 7 days after surgery. Serum concentrations of interleukin-6 (IL-6), interleukin-1 (IL-1), interleukin-10 (IL-10) and prolactin were determined using enzyme-linked immunosorbent assay. Cortisol and GH concentrations were determined by radioimmunoassay. RESULTS: Twenty-four hours after surgery, prolactin, GH and cortisol levels were higher than preoperative values in both OC and LC groups. Seven days after surgery, cortisol and GH levels had normalized but prolactin levels were maintained. No significant differences in hormone levels were detected between OC and LC groups. IL-6 levels were significantly higher in the OC group 7 days after intervention. Correlation analysis between levels of cytokines and hormones indicated that prolactin, at concentrations exceeding physiological values, regulates levels of IL-1 (p 0.3271, p < 0.05) and IL-6 (p = 0.3765, p < 0.01). Although levels were similar in both groups, cortisol was shown to exert weak but significant, linear control on IL-6 levels (r = 0.4569, p < 0.001). CONCLUSIONS: A similar hormonal response to surgical insult was produced in patients subjected to OC and LC. IL-6 levels seem to be the most indicative of injury. Prolactin is the main hormone involved in the regulation of cytokines produced in response to this type of stress and is thought to exert control over the production of IL-6.

Adult↗