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Biomedical subjects

A Sánchez-Ibarrola

Publications and source records attributed to A Sánchez-Ibarrola.

At least 19 recordsLinked to original sources
PubMed2004

Anti-inflammatory cytokines induce lipopolysaccharide tolerance in human monocytes without modifying toll-like receptor 4 membrane expression.

Toll-like receptor 4 (TLR4) participates in innate immunity by detecting lipopolysaccharides (LPS) of Gram-negative bacterial cell walls. TLR4 macrophage expression in mice is modulated by LPS. This fact constitutes, at least partially, the molecular basis for LPS tolerance. Very recently, the effect of interferon-gamma (IFN-gamma), a pro-inflammatory cytokine, has been described on TLR4 membrane expression of human monocytes. IFN-gamma up-regulates TLR4 expression and antagonizes the LPS-induced TLR4 down-regulation. These data prompted us to study the expression of membrane TLR4 in human mono- cytes in which LPS tolerance was induced by LPS and by anti-inflammatory cytokines [interleukin-10 (IL-10) and transforming growth factor beta1 (TGFbeta1)]. Data concerning this latter model, and more specifically, the effect of anti-inflammatory cytokines over TLR4 expression, are not available at present. We show here that membrane TLR4 expression in human monocytes falls after LPS exposure. The effect was prolonged for 12 h, but then expression returned to normal levels. The incubation of human monocytes with IL-10, TGFbeta1 or a mixture of both induces no alterations in membrane TLR4 expression. However, these cytokines are able to substitute the tolerizing LPS exposure in order to induce LPS tolerance. Our data help to achieve a better understanding of the way cytokines control the cellular expression of TLR.

Adult↗
PubMed2000

The increase of IFN-gamma production through aging correlates with the expanded CD8(+high)CD28(-)CD57(+) subpopulation.

The use of flow cytometry to detect intracellular cytokines at the single cell level has the potential to quantify cytokine production together with the possibility of phenotypic identification of the cell population concerned. The unbalanced presence of intracellular cytokines produced by T cells has been recognized in some pathological conditions. To better address this issue, we studied the production of IFN-gamma and IL-4 in CD4(+) and CD8(+high) T cells in healthy donors of a broad range of age (17-62 years). Given that an increase of IFN-gamma and IL-4 with aging had been reported by some authors in healthy controls, we have performed a multivariate analysis to assess the intrinsic role of aging or of other external factors, such as chronic antigenic exposures (i.e., viruses), over the cytokine production of phenotypically characterized T cells. In this respect we show that, mainly in CD8(+high) T cells, the production of IFN-gamma is directly correlated with age. Besides, the cytokine production correlates with the CD8(+high)CD28(-)CD57(+) T-cell population, which we have recently reported elevated in aged individuals. Perhaps this T-cell subpopulation plays a regulatory role as a Tc1 response in aging individuals.

Adolescent↗
PubMed1999

Cytokine flow cytometry differentiates the clinical status of multiple sclerosis (MS) patients.

In this study we have examined intracellular cytokines in peripheral blood mononuclear cells (PBMC) of MS patients by flow cytometry (cytokine flow cytometry). MS progressive patients showed an increased number of cells producing interferon-gamma (IFN-gamma) after activation with phorbol 12-myristate 13-acetate and ionomycin, compared with patients with clinically inactive forms (P < 0001) and with healthy controls (P = 0001). These cells belonged to the CD4+ and CD8+ subsets in similar proportions. Clinically inactive patients showed a lower level of cells producing IL-2 than controls (P = 0.03) and active MS patients (P = 0.03). Most IL-2-producing cells were CD4+ lymphocytes, although a small part of the IL-2 was also produced by CD8+ cells. The percentage of cells producing simultaneously IL-2 and IFN-gamma was increased in active MS and they were mainly CD4+ lymphocytes. No differences in the production of IL-4 were observed between groups. However, we found an increased IL-10 production in clinically active MS patients (P = 0.03). Treatment with IFN-beta of active MS patients showed lower levels of cytokines when compared with untreated MS patients. This methodological approach could help in the follow up and therapeutic monitoring of MS patients.

Adult↗
PubMed1999

CD5 and CD23 expression on B cells in peripheral blood and synovial fluid of rheumatoid arthritis patients: relationship with interleukin-4, soluble CD23 and tumour necrosis factor alpha levels.

METHODS: We have studied in peripheral blood (PB) and synovial fluid (SF) of 31 patients diagnosed with rheumatoid arthritis (RA), the expression of CD5 and CD23 antigens on B cells, and the levels of soluble CD23 (sCD23), interleukin-4 (IL-4) and tumour necrosis factor alpha (TNF-alpha). We have also correlated the results with the disease activity index. RESULTS: CD5+ B cells are expanded in SF and, moreover, show higher expression of CD23 than CD5 - B cells. Twelve patients had detectable levels of IL-4 in plasma and 10 in SF (nine patients in both samples); the absence of IL-4 was related to a higher expression of CD23 on CD5 + B cells and with higher levels of sCD23. A negative correlation was found in SF between TNF-alpha and sCD23 levels. CONCLUSION: There is no correlation between disease activity index and the different parameters studied (expression of CD5 and CD23 on B cells, sCD23, IL-4 and TNF-alpha levels) either in plasma/PB or in SF.

Arthritis, Rheumatoid↗
PubMed1998

Progressive decrease of CD8high+ CD28+ CD57- cells with ageing.

An age-dependent decrease in T cell responsiveness to CD28 costimulation has been described. In order to test the hypothesis that an age-related decrease in CD28 expression by CD8+ T lymphocytes might be involved, we analysed 67 healthy donors ranging in age from 15 to 69 years for their CD8+ T cell expression of CD28 and CD57. We found a statistically significant decrease of CD28 expression through ageing and a significant increase of CD57 expression, both markers being mutually exclusive. Given that cytomegalovirus (CMV) is reported to induce CD57 expression, and since the carrier status for this ubiquitous virus increases with age in the general population, it seemed essential to evaluate whether the phenotypic age-related changes described in CD8high+ cells were not influenced by the CMV carrier status of the individuals. Accordingly, we performed a multivariate analysis to assess the independent association of age and CMV carrier status with CD28 and CD57 expression in CD8high+ cells. Results showed that the progressive decrease in CD8high+ CD28+ CD57- cells was associated only with age, while the expansion of the CD8high+ CD28- CD57+ subset depended both on age and CMV, although mainly on age. We conclude that ageing is accompanied by a progressive loss of CD28 expression in CD8+ T cells and a reciprocal enhancement of CD57 expression, both facts being probably related to the repeated antigenic stimulation occurring throughout life.

Adolescent↗
PubMed1992

The measurement of transforming growth factor type beta (TGF beta) levels produced by peripheral blood mononuclear cells requires the efficient elimination of contaminating platelets.

In recent years there has been an increasing interest in measuring the levels of TGF beta produced by peripheral blood mononuclear cells (PBMC), since its abnormal regulation seems to be involved in several pathological states. Platelet-contamination, a common feature in PBMC populations isolated by the standard Ficoll-Paque method, would theoretically disturb the measurement of the levels of TGF beta produced by mononuclear cells, since platelets represent an important source of this cytokine. In this study, supernatants of PBMC cultures from healthy subjects, either platelet-contaminated or uncontaminated, were assayed for TGF beta activity in three different bioassays. We report that the presence of platelets led in most cases to an important overestimation of the TGF beta levels produced by MNC in the Swiss-3T3 bioassay and in a PBMC proliferation assay. In contrast, in the Mv1Lu bioassay these levels were significantly underestimated, an effect which we attribute to the presence of other platelet-derived growth factors. These results suggest that the elimination of platelets from PBMC cultures is essential if TGF beta production by mononuclear cells is to be studied.

Biological Assay↗
PubMed1990

Insulin requirements and residual beta-cell function 12 months after concluding immunotherapy in type I diabetic patients treated with combined azathioprine and thymostimulin administration for one year.

An increase in clinical and functional remissions with immunosuppression, as well as abnormal T-cell function, in Type I diabetic patients has been reported in the early stages of diabetes. A controlled trial with azathioprine and thymostimulin in separate and combined administration was performed in 45 recently diagnosed Type I diabetic patients. Phenotyping of the T-lymphocyte subsets, levels of CD25 positive cells and interleukin-2 production by patients' lymphocytes, as well as remission rate and stimulated C-peptide levels, were serially assessed. Remission was defined as mean weekly glycemic profiles less than or equal to 7 mmole/l, serial HbA1 values in the normal range and no insulin requirements for at least 2 consecutive months. At 3,6,9 and 12 months of immunotherapy, remission occurred respectively in 0%, 8.3%, 16.6% and 0% of the conventionally treated diabetic controls and in 42.8%, 50%, 42.8% and 36.2% of the subjects submitted to combined azathioprine and thymostimulin administration. Patients receiving azathioprine or thymostimulin alone did not achieve better remission rates than controls. C-peptide levels were significantly higher (above 0.6 pmol/ml) in patients with remission than in those not in remission (P less than 0.02) throughout the trial. Excessive interleukin-2 production in recently diagnosed diabetics returned to normal levels in patients in remission. In the group receiving combined therapy, 38.5%, 25% and 23% were still in clinical remission at 6, 9 and 12 months after drug withdrawal. Twelve months after stopping treatment, patients who had remitted exhibited significantly lower insulin requirements and greater endogenous insulin secretion than those who had not remitted; the former also maintained near normal glycemic control. No side effects were detected except mild and transient leucopenia in a reduced number of patients receiving azathioprine. Remission was related to the time of beginning immunotherapy after the onset of diabetes (17.1 +/- 7 vs 42.5 +/- 15 days; P less than 0.01) and to age (17.7 +/- 5.6 vs 13 +/- 7 years; P less than 0.05). Interleukin-2 production seems to be negatively associated with clinical remission in the early stages of diabetes. Results suggest a complementary effect of the drugs used in this study that may enhance long-term remission in recently diagnosed Type I diabetic patients.

Adolescent↗
PubMed1989

[Changes caused by staphylococcal protein A and gamma interferon on the natural cytotoxic activity in patients with cancer].

The effects on natural killer (NK) activity of in vitro incubation of effector cells with staphylococcal Protein A (SPA) and gamma interferon (gamma IFN) in patients with different types of tumors have been compared. The modifications induced in NK activity by these two immunomodulators were assessed using the K-562 cell line and autologous tumoral cells as targets of natural cytotoxicity. The results obtained show that both SPA and gamma-IFN are good inducers of NK activity against the K-562 cell line. SPA always shows itself more efficient than gamma-IFN in increasing the basal level of NK activity. The cytotoxicity against autologous tumoral cells was also greatly increased by the two immunomodulators assayed, SPA being also in this type of assay more efficient than gamma-IFN. Taken the data as a whole the increases induced by SPA and gamma-IFN are parallel both against K-562 and autologous tumoral cells. However when the different types of tumours are considered separately some discrepancies between NK activity against K-562 and autologous tumoral cells appear. The effects of SPA as a modifier of NK activity against autologous tumoral cells looks clear. In our experiments incubation of effector cells with SPA behaves more effectively than the well established gamma-IFN model in the induction of this type of activity. The intimate mechanisms by which SPA exerts its action are quite interesting and merit further investigation.

Cells, Cultured↗
PubMed1989

[Role of the contact plasma system in human physiopathology].

The possible implications of the plasma contact system in several human pathological conditions have been reviewed. The mechanism of activation and the biochemistry of the different components of this physiological system are described. The activation of the plasma contact system and its important physiological consequences are considered. The implication of the plasma contact system in the pathogenesis of different human and experimental pathological conditions (shock, disseminated intravascular coagulation, extracorporeal circulation...) is reviewed. A particular consideration is given to the pathogenesis of glomerulonephritis where the plasma contact system has been more directly implicated.

Factor XI↗
PubMedDate not supplied

Subacute cutaneous lupus erythematosus--clinical, histopathological and immunophenotypical study of five cases.

Subacute cutaneous lupus erythematosus (SCLE) is a recently described distinct subset of lupus erythematosus (LE) having characteristic clinical, serological and genetic features. The clinicopathological and serological findings of 5 patients are reported. From a clinical point of view, we describe two types of cutaneous lesions: psoriasiform and annular pattern. ANA were present in 80% of the cases, anti-Ro was present in 60%, and anti-La in 20%; anti-RNP was positive in 1 patient. Circulating immune complexes were detected in 2 patients, and low levels of complement factors (C3, C4) in another 2 patients. The B- cell alloantigens HLA-A2, HLA-Bw4 or HLA-DR3 were present in 60% of the cases. The cutaneous histopathology revealed important changes in the epidermis. Our findings are similar to those described by most other authors. Also, we would like to emphasize the low disease activity and benign course of our patients.

Adult↗
PubMedDate not supplied

[Cytokines-endothelium interaction: its role in the thrombotic process].

The in vivo relationship between the immune and the coagulation systems is a well documented fact. In a number of pathological conditions, thrombosis is not understood isolately, but in the context of inflammation and immunity. The mediators in these complex multidirectional interactions are the cytokines, a group of soluble peptides which act on surface cellular receptors, with immunoregulatory properties. These molecules influence negatively the physiological antithrombogenic situation by two different mechanisms. They are involved in processes which disrupt the endothelial integrity, and at the same time, they are capable of activating the endothelium in a prothrombotic manner, by stimulating procoagulant activities and by inhibiting different anticoagulants.

Arteriosclerosis↗
PubMedDate not supplied

[Toll type receptors: molecular bases of the relationship between innate and adaptation responses of the immune system].

Microbes have on their surface molecular patterns that are common among a broad range of pathogens. These patterns are recognized by a wide variety of cellular receptors, the most important of which are a family of transmembrane proteins termed "Toll-like receptors" (TLR). TLRs are pattern-recognition receptors that have key roles in detecting pathogens and initiating inflammatory responses. The receptor of Gram negative bacterial LPS, TLR4, is the best characterized member of the TLR family. So far, ten mammalian toll-like receptors (TLR1-TLR10) have been identified. Recent studies revealed that the TLR signaling pathway is a critical mediator of sepsis. An understanding of TLRs and their signaling pathway will reveal a therapeutic target in sepsis and other immune mediated diseases.

Animals↗
PubMedDate not supplied

[Past, present and future of anti-idiotype vaccination].

Cancer vaccines are conceived as therapeutic tools, in contrast to the prophylactic vaccines used to fight against infectious diseases. Among the most potent therapeutic vaccines, anti-idiotype vaccination is directed against the tumor idiotype, the only well-characterized tumor antigen displayed in neoplastic B-cells. Anti-idiotype vaccines have demonstrated clinical benefit against follicular lymphoma and are currently being evaluated in two different phase III clinical trials. Additional emerging strategies, which include the use of dendritic cells and the production of vaccines via molecular means will surely allow us to draw important conclusions concerning the treatment of cancer patients.

Cancer Vaccines↗
PubMedDate not supplied

HLA in allergic twins.

Interest in the study and determination of the influence of a genetic factor in the etiology of bronchial asthma was initiated by Cook. This is a study of 13 pairs of twins that were seen in our department presenting some kind of allergic illness. Each pair of twins underwent a complete clinical history and physical examination, routine laboratory analysis and radiography. In addition, they were also tested for the following: skin test, serum immunoglobulins, total IgE, histamine release test, hemagglutination test, histocompatibility antigen (HLA). Statistical analysis was done using the Chi square test, with significant results found in 4 antigens, namely A2, A30 + 31, B5 and B12.

Adolescent↗
PubMedDate not supplied

[Detection and clinical evaluation of antibodies against soluble nuclear antigens].

The presence of anti-nuclear antibodies (ANA) is particularly common in the group with so-called "systemic rheumatic disease". Routinely these antibodies are detected by indirect immunofluorescence techniques using different substrates since they are non-organ and non-species specific. Nowadays the detection o ANA in a particular patient is not enough further study must be done to identify the antigen responsible for that pattern. Many different nuclear antigens have been described. In this review, we comment on the detections, clinical significance and incidence of antibodies produced against certain specific nuclear antigens: the saline extractable nuclear antigen (ENA). These antigens have been detected indirectly by using immunodiffusion, counterimmunoelectrophoresis by bringing into contact the patient's serum and nuclear antigenic extracts from different sources.

Antibodies, Antinuclear↗
PubMedDate not supplied

A triple autoimmune association.

We present a female patient affected by the triple association of rheumatoid arthritis, amyloidosis and Sicca Syndrome. The individual pathological features are well documented. We discussed the rarity of this presentation and some pecularities of the case such as the presence of a true Sicca Syndrome with lymphoid infiltration of the salivary glands to distinguish it from other amyloid patients with Sicca Syndrome due to the infiltration of exocrine gland by amyloid.

Amyloidosis↗