Biomedical subjects

M al-Janadi

Publications and source records attributed to M al-Janadi.

15 recordsLinked to original sources

PubMed1996

Interleukin-10 (IL-10) secretion in systemic lupus erythematosus and rheumatoid arthritis: IL-10-dependent CD4+CD45RO+ T cell-B cell antibody synthesis.

Interleukin-10 (IL-10) is a major immunoregulatory cytokine and has a multitude of immunomodulatory effects in the immune system. In this study, we have examined the secretion and in vitro function of IL-10 in B cell hyperactivity in antibody production in two common autoimmune diseases, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). IL-10 was detectable in serum of all active SLE and serum and synovial fluid samples of all RA patients but in none of the normal controls. B cells and CD4+CD45RO+ "memory" T cells secreted highly enhanced levels of IL-10 in SLE and RA versus normals. Increased IgM and IgG production by B cells-CD4+CD45RO+ T cells in SLE and RA was IL-10 dependent, since neutralization of IL-10 cytokine by anti-IL-10 antibody drastically reduced Ig synthesis in these coculture experiments. B cell hyperactivity in autoantibody production in SLE and RA may be a function of IL-10-dependent CD4+CD45RO+ Th2 cell activation. Therefore, IL-10 may play an important role in highly disturbed immune system and B cell-T cell function in these immune disorders.

Adolescent↗

PubMed1995

CD4+ Th2 cell response cytokine production in bacterial meningitis.

There has been a growing body of evidence suggesting that CD4+ Th1/Th2 cell responses participate in pathologic and immunologic processes in infectious disease. Bacterial meningitis is a fatal disease of children and is associated with a spectrum of clinical syndromes. This study provides evidence of CD4+ enhanced interleukin (IL)-4 and IL-6 but decreased IL-2 and interferon-gamma (IFN-gamma) production, the induction of characteristic Th2 cell response cytokines in bacterial meningitis, which may play an important role in disease mechanism. Additionally, monocyte-induced enhanced IL-6, IL-8, and tumor necrosis factor-alpha production may be associated with distinct clinical features such as fever, seizures, and neurological sequelae. A striking finding was also the highly deficient monocyte-induced granulocyte-macrophage colony-stimulating factor production. Of particular interest, the CD(8+)-enhanced IFN-gamma production may be required for the cytolytic activity or protective response to be maintained in this disease. Taken together, these data reveal that monocytes and CD4+ (Th2) and CD8+ subsets produce distinct cytokines in bacterial meningitis, which may exert an immunoregulatory and immunopathologic effect and thus mediate some of the clinical manifestations of the disease.

CD8-Positive T-Lymphocytes↗

PubMed1995

Enhanced interleukin 8 secretion in circulation of patients with Behçet's disease.

OBJECTIVE: The pathogenesis of Behçet's disease (BD) has not yet been determined. Several hypotheses have been postulated and cytokines that control growth proliferation and hematopoiesis of progenitor cells play a role in relation to immune response and inflammatory dysfunction. We investigated whether cytokines play a role in pathogenesis of BD. METHODS: We employed the quantitative sandwich enzyme immunoassay technique, in which antibody is already coated on the microtiter plate standard and samples are pipetted into the wells. Antigen present is bound by immobilized antibody. After incubation and washing steps, conjugate, which is enzyme linked polyclonal antibody specific for the antigen is added to the wells. Following a wash to remove any unbound antibody enzyme reagent, a substrate solution is added to the wells, and color develops in proportion to the antigen bound in the initial steps, which can be read in terms of optical density present in the standards and in the samples. RESULTS: Of a total of 53 samples with BD, 33 (64%) had detectable levels of interleukin 8 (IL-8). Levels of IL-6, tumor necrosis factor alpha and interferon-gamma were not significantly elevated in patients with BD. CONCLUSION: We found that IL-8 levels are higher in patients with active BD, and since IL-8 has a potent effect on the neutrophil, this cytokine most likely participates in the inflammatory response of this disease.

Behcet Syndrome↗

PubMed1994

Circulating levels of cytokines and soluble cytokine receptors in various T-cell malignancies.

BACKGROUND: Cytokines, interleukin (IL)-4, IL-6, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), soluble CD23 (sCD23), and soluble IL-2 receptors (sIL-2R) are mediators of inflammation and immune response. Alterations in immune status of patients with various cancers may result in release of cytokines in circulation. The authors measured the circulating levels of IL-4, IL-6, IFN-gamma, TNF-alpha, sCD23, and sIL-2R from patients with T-cell chronic lymphocytic leukemia (T-CLL), T-cell acute lymphoblastic leukemia (T-ALL) and peripheral T-cell lymphoma (PTCL) to determine their importance in these T-cell disorders. METHODS: IL-4, IL-6, IFN-gamma, TNF-alpha, sCD23, and sIL-2R levels were measured from the serum samples by enzyme-linked immunosorbent assay or bioassay methods. RESULTS: IL-4 levels were higher only in T-CLL, whereas, IFN-gamma and sIL-2R levels were higher in T-CLL and T-ALL. However, IL-6, TNF-alpha, and sCD23 levels were higher in PTCL. CONCLUSIONS: T-cell-derived IL-4 and IFN-gamma in T-CLL may act as an autocrine growth factor for proliferation of neoplastic T-cells. The sIL-2R levels in T-CLL, T-ALL, and PTCL are an indication of the degree of T-cell or immune activation due to concomitant immunologic processes in these disorders. However, IL-6, TNF-alpha, and sCD23 levels may contribute to inflammatory response and provide evidence of monocyte/macrophage, T-cell, or B-cell aberrations in PTCL.

Adolescent↗

PubMed1994

Soluble CD23 and interleukin-4 levels in autoimmune chronic active hepatitis and systemic lupus erythematosus.

A variety of cytokines secreted by cells of the immune system could contribute to the induction or persistence of the inflammatory processes in autoimmune and infectious diseases. Soluble CD23 (sCD23) and interleukin-4 (IL-4) are the recently characterized factors implicated in B cell-T cell function in human disease. In this study we examined the circulating levels of sCD23, IL-4, and soluble interleukin-2 receptors (sIL-2R) from patients with hepatitis B surface antigen-positive (HBsAg+) acute viral hepatitis (AVH), HBsAg+ chronic active hepatitis (HBsAg+ CAH), and autoimmune chronic active hepatitis (AICAH) and from autoimmune rheumatic disease patients, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The sCD23 was found in sera from 16 of 16 patients with AICAH (159.0 +/- 40.8 ng/ml), in 3 of 32 patients with AVH (4.1 +/- 15.6), 5 of 30 patients with HBsAg+ CAH (6.9 +/- 17), 8 of 25 patients with SLE (19.4 +/- 37.2), 2 of 21 patients with RA (4.7 +/- 16.3), and none of the 50 age-matched healthy controls. However, sIL-2R was detected more frequently in sera from all hepatitis and rheumatic disease patients. In AICAH, sCD23 levels correlated positively with IL-4 (r = 0.44, P = 0.001) but not with sIL-2R. Markedly elevated levels of sCD23 and IL-4 in serum are prominent and characteristic features of AICAH disease, which could play an important role in the pathogenesis or induction and perpetuation of the inflammatory response in this disorder.

Adult↗

PubMed1994

Gamma delta T lymphocytes and proinflammatory cytokines in bacterial meningitis.

BACKGROUND: Patients with bacterial meningitis have a T-cell defect and impaired cytokine production. METHODS: The phenotype and percentage of circulating alpha beta and gamma delta T-cell receptor-bearing lymphocytes were determined from patients with bacterial meningitis (Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis), patients with bacterial infection but without meningitis, and healthy control subjects by a monoclonal antibody staining method. The in vitro production of cytokines, interleukins (IL-2, IL-6), interferon-gamma and tumor necrosis factor-alpha was measured by the bioassay or ELISAs. RESULTS: The percentage of circulating gamma delta T cells with a CD3+CD4+CD8- phenotype was significantly (p < 0.001) increased in all patients with bacterial meningitis compared with patients with bacterial infection and healthy control subjects. The CD3+ gamma delta T cells from patients with meningitis produced highly elevated levels of two proinflammatory cytokines, tumor necrosis factor-alpha and IL-6. However, interferon-gamma production was enhanced by CD3+ alpha beta T cells. CONCLUSION: The increased percentage of circulating T-cell receptor gamma delta T cells and their in vitro production of tumor necrosis factor-alpha and IL-6 cytokines may play an important role in the pathogenesis and inflammatory response in bacterial meningitis.

Antibodies, Monoclonal↗

PubMed1994

Immunoregulatory and proinflammatory cytokine production in visceral and cutaneous leishmaniasis.

Visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL) are the major parasitic diseases in which the immune system is implicated in pathogenesis. The in vitro production of interleukin (IL)-2, IL-4, IL-6, IL-8, tumor necrosis factor-alpha (TNF alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF), spontaneously and in response to stimulation of peripheral blood mononuclear cells with anti-CD3, phytohemagglutinin, and lipopolysaccharide, was investigated to determine their importance in VL and CL. Highly enhanced production of IL-4, IL-6, IL-8, and TNF alpha was seen in VL. However, enhanced production of IL-4 and TNF alpha but almost normal production of IL-6 and IL-8 was seen in CL. The highly increased IL-4 production was the most characteristic and common feature of both VL and CL. Of interest, highly deficient GM-CSF production may be implicated in abnormalities in synthesis of hematopoietic lineage of cells in these diseases.

Cells, Cultured↗

PubMed1993

Peripheral T-cell lymphoma with unique immunologic features.

BACKGROUND: The autologous mixed lymphocyte reaction (AMLR) is an important immunoregulatory phenomenon in human immune disorders. The authors have determined the phenotype and assessed the response of malignant lymph node T-cells, from histologically and immunologically proven cases of peripheral T-cell lymphoma, in AMLR and allogeneic mixed lymphocyte reaction (MLR) and studied the secretion of lymphokines. METHODS: The proliferative response, tritiated 3H-thymidine incorporation assay, was used to determine the AMLR and allogeneic MLR of the responding T-cells. An interleukin-2 (IL-2)-dependent T-cell line (CTLL) was used for the production of IL-2 by phytohemagglutinin-stimulated T-cells in a cytotoxic assay. B-cell growth and differentiation factor activity of T-cells was studied by enzyme-linked immunosorbent assay. RESULTS: The AMLR of malignant lymph node T-cells was increased characteristically in 12 of the 14 lymphoma cases studied; however, that of the blood T-cells was decreased. The allogeneic MLR of the malignant lymph node T-cells and blood-purified T-cells of the eight cases investigated was decreased. Expression or deficiency of CD2 and CD3 antigens on malignant T-cells did not show any difference in the AMLR assay. CONCLUSIONS: This study demonstrates an important tendency of malignant T-cells from patients with peripheral T-cell lymphoma to proliferate in AMLR. The highly augmented AMLR but deficient allogeneic MLR observed in these malignant T-cells indicate that autologous recognitive events may play an important role in the immunopathogenesis of this human disease.

Adult↗

PubMed1993

Cytokine profile in systemic lupus erythematosus, rheumatoid arthritis, and other rheumatic diseases.

We investigated serum levels of interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and tumor necrosis factor alpha (TNF alpha) from patients with systemic lupus erythematosus (SLE) and its various clinical manifestations of disease and from patients with rheumatoid arthritis (RA) and other rheumatic diseases. The serum levels of IL-6 and IFN-gamma were highly elevated from patients with SLE associated with lymphadenopathy (LN) or nephrotic syndrome (NS). On the contrary, the serum levels of TNF alpha were elevated from most patients with SLE associated with thrombocytopenia (TP). However, serum levels of TNF alpha were in the normal range from patients with SLE associated with NS, LN, or central nervous system disease. Of interest, patients with SLE associated with humoral immunodeficiency disorder, hypogammaglobulinemia, had highly elevated levels of serum IL-6. The concanavalin A-stimulated mononuclear cells (MNC) of patients with SLE associated with TP secreted highly elevated levels of TNF alpha compared to other patient groups. We suggest that abnormal production of various cytokines in SLE is an intrinsic defect of MNC and the immune system that may be the key element for a variety of clinical manifestations of this disease.

Adolescent↗

PubMed1993

Cytokine profile of viral and autoimmune chronic active hepatitis.

BACKGROUND: Patients with hepatitis have multiple immunologic abnormalities, which may be related to cytokine production. METHODS: We examined the in vitro production of interleukins (IL-2, IL-4, IL-6), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) in purified peripheral blood mononuclear cells (PBMCs) of patients with hepatitis B virus positive (HBV), acute viral hepatitis (A-HBV), HBV + chronic active hepatitis (HBV-CAH), and autoimmune-type chronic active hepatitis (AI-ACH). RESULTS: IFN-gamma and TNF-alpha production were characteristically higher in patients with A-HBV than in healthy control subjects (p < 0.001). However, patients with AI-CAH produced highly elevated levels of IL-4 and IL-6 compared with patients with A-HBV and HBV-CAH and healthy control subjects. The cytokine profile (PBMC-induced IL-2, IL-4, IL-6, IFN-gamma, and TNF-alpha production) is different in A-HBV, HBV-CAH, and AI-CAH disease. The increased cytokine secretion (IFN-gamma and TNF-alpha in A-HBV and IL-4 and IL-6 in AI-CAH) could reflect altered relative frequencies of different cell phenotypes in these diseases. CONCLUSIONS: Specific cytokine production may be important in the pathophysiology associated with diverse inflammatory states in patients with hepatitis.

Adult↗

PubMed1993

B cell hyperactivity is a function of T cell derived cytokines in systemic lupus erythematosus.

OBJECTIVE: T cell abnormalities and abnormal production of cytokines is a key event of B cell hyperactivity and antibody synthesis in systemic lupus erythematosus (SLE). We investigated T cell function and role of interleukin 4 (IL-4) and IL-6 in B cell induced Ig synthesis from SLE. METHODS: Phenotypes and expression of activation antigens on T cells and monocytes was determined by specific monoclonal antibodies using indirect immunofluorescence technique. IL-4, IL-6 and tumor necrosis factor-alpha (TNF alpha) assays and in vitro Ig synthesis was carried out by enzyme linked immunosorbent assays. RESULTS: CD25, CD38 and CD71 expressing T cells and monocytes were increased in circulation of patients with SLE. Patients with SLE associated with prominent clinical presentation like lymphadenopathy had a higher percentage of gamma delta T cells in blood. CD4+CD29+ T cell subsets, which were the major T cells secreting IL-6, were increased in the circulation and provide effective helper function to B cells in their enhanced in vitro Ig synthesis in SLE. CONCLUSION: Our results demonstrate that CD4+CD29+ T cell subsets produced elevated levels of IL-6 in SLE and that IL-6 overproduction may contribute to the B cell hyperactivity in enhanced antibody synthesis characteristic of this autoimmune disease.

ADP-ribosyl Cyclase↗

PubMed1993

Cytokine production by helper T cell populations from the synovial fluid and blood in patients with rheumatoid arthritis.

OBJECTIVE: Our study was undertaken to determine the phenotypic changes and cytokine production from the synovial fluid (SF) and blood of patients with rheumatoid arthritis (RA). METHODS: Blood and SF purified T cells were stained with monoclonal antibodies using standard, indirect immunofluorescence technique for the determination of T cell receptor (TcR) TcR alpha beta and TcR gamma delta antigen expressions, CD25, CD38, CD71, HLA-DR activation antigens, and for percentage distribution of CD4+CD29+ and CD4+CD45RA+ subsets. The production of interleukin 2 (IL-2), IL-4 and IL-6 by various T cell compartments was determined by the bioassay or enzyme linked immunosorbent assay methods. RESULTS: Highly elevated percentage of CD3+TcR gamma delta and CD4+CD29+ T cell subsets were detected in SF and blood of RA. The CD4+CD29+ T cell subsets produced elevated levels of IL-4 and IL-6 but deficient levels of IL-2. IL-6 cytokine induced CD4+CD29+ subsets were found to provide effective helper function to B cells in IgG and IgM synthesis. CONCLUSION: The IL-6 production and IL-6 induced CD4+CD29+ T cell subset function in B cell antibody synthesis may be important in B cell hyperactivity and antibody synthesis in RA. Our studies suggest that CD4+CD29+ subsets bearing TcR gamma delta antigens are increased at inflammation site (SF) in RA and is implicated in immunopathology and autoantibody production of this inflammatory condition in humans.

Antigens, CD↗

PubMed1993

Visceral leishmaniasis: II. Histiocyte ultrastructure in bone marrow associated with low level of parasitaemia and mimicking malignant histiocytosis.

The ultrastructural features of histiocytes in the bone marrow (BM) were studied in a febrile, splenomegalic and pancytopenic Sudanese patient who was diagnosed by one of us as visceral leishmaniasis (VL) associated with low level of parasitaemia and mimicking malignant histiocytosis (MH). Serial thick (STS) and ultrathin (SUT) sections showed that the BM was hypercellular and markedly infiltrated by large histiocytes with prominent phagocytosis. A thorough examination of various ST and UT section revealed only a single, typical Leishman-Donovan body. At transmission electron microscopy (TEM) level, two principal types of histiocytic cells were identified: Type I, subdivided into two subtypes, were actively phagocytic histiocytes (PH) with large digestive vacuoles and primary lysosomes; type II were nonphagocytic histiocytes (nPH) with primary lysosomes only. The rate of PH to nPH ws 7:2 in plastic STS. The interaction between the PH and ingested cells is described. Both types of cell were morphologically similar to previously described malignant histiocytic cells. However, this study showed a better characterization of PH during VL.

Adult↗

PubMed1992

Gamma delta T cells and the immune response in visceral leishmaniasis.

Visceral leishmaniasis (VL) caused by Leishmania donovani, a protozoan parasite, is a disease of high morbidity associated with hepatosplenomegaly, hypergammaglobulinemia, fever and death. One of the immunological hallmarks of VL is a remarkable increase in serum immunoglobulin levels as a result of polyclonal B cell activation. This study demonstrated that T lymphocytes expressing the T cell receptors (TcR) gamma delta in association with CD3 molecules are increased in circulation of patients with VL. A large proportions of TcR gamma delta-bearing T cells had CD4+ CD8- phenotype, and expressed CD25, CD38, CD71 and HLA-DR activation antigens. Furthermore, we demonstrated wide functional differences in TcR gamma delta and TcR alpha beta T cells in their proliferative response, secretion of interleukin-2 (IL-2), B cell growth factor (BCGF) and B cell differentiation factor (BCDF). It was of interest that the TcR gamma delta T cells from patients with VL could be expanded by in vitro culture with human recombinant IL-2. Although these TcR gamma delta T cells secreted diminished levels of IL-2, they produced highly augmented levels of both BCGF and BCDF, suggesting that secretion of these lymphokines in these T cell subsets is regulated independently. The relative increases in the CD4+ CDw29+ TcR gamma delta T cell subsets and their secretion of highly elevated levels of BCGF and BCDF largely accounted for the humoral immune system abnormality and hypergammaglobulinemia found in this disease. These observations may help to explain that TcR gamma delta T cells might be functional in vivo and are involved in immunological mechanisms of pathogenesis in VL.

Antigens, CD↗

PubMed1989

Cyclophosphamide treatment of interstitial pulmonary fibrosis in polymyositis/dermatomyositis.

Interstitial pulmonary fibrosis is a serious complication of inflammatory muscle disease associated with significant morbidity and mortality. We describe 3 consecutive cases complicating dermatomyositis (1 case, anti-Jo-1 antibody negative) and polymyositis (2 cases, anti-Jo-1 antibody positive) in which cyclophosphamide was added to prednisone therapy with favorable outcomes.

Adult↗