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Biomedical subjects

S Raziuddin

Publications and source records attributed to S Raziuddin.

At least 19 recordsLinked to original sources
PubMed1998

A mixed Th1/Th2 cell cytokine response predominates in systemic onset juvenile rheumatoid arthritis: immunoregulatory IL-10 function.

The immune response identified by the induction of Th1/Th2 cells plays a critical role in the pathogenesis of various inflammatory and immune disorders. We have determined that in children with systemic onset juvenile rheumatoid arthritis (JRA), peripheral blood mononuclear cells (PBMC) constitutively and after stimulation with various antigens in vitro induce a higher secretion of interleukin-4 (IL-4) and IL-10 with a characteristic deficiency of IL-2 and interferon-gamma (IFN-gamma). This cytokine pattern is a representative of a mixed Th1/Th2 cell response in JRA. The CD3/CD28 costimulatory molecule was found to be a potent inducer of IL-4 and IL-10 secretion. PBMC-derived augmented IL-10 secretion was inhibited by exogenous Th1 cell type recombinant cytokines (IL-2, IL-12, and IFN-gamma). Although IL-10 inhibits PBMC-induced proinflammatory IL-1alpha and tumor necrosis factor-alpha secretion, it had no major effect on IL-6 production. The finding of a distinctly enhanced mixed Th1/Th2 cell response cytokine (IL-4 and IL-10) pattern in JRA provides a framework for developing strategies for immunologic intervention in this rheumatic disorder in children.

Arthritis, Juvenile↗
PubMed1998

Regulation of interleukin-4 production and cytokine-induced growth potential in peripheral T-cell non-Hodgkin's lymphomas.

The malignant cells in tumour tissues produce cytokines/growth factors that may influence tumour growth, tumour immunogenicity and host immune response. We demonstrate that lymph node cell (LNC) purified neoplastic T cells from CD4+ peripheral T-cell lymphoma (CD4+ PTCL) and CD8+ PTCL spontaneously, and after stimulation with anti-CD3, secreted high amounts of interleukin-4 (IL-4) as compared to LNC-purified CD4+ and CD8+ non-malignant T cells. Furthermore, IL-4 was observed to be the most potent cytokine that induced in vitro proliferation and growth of the malignant T cells. Moreover, malignant T-cell-derived IL-4 secretion was augmented by exogeneous recombinant human interferon-gamma (IFN-gamma) and was profoundly inhibited by IL-2. Because IL-4 was shown to be a locally active cytokine with a wide range of immunoregulatory properties, regulation of IL-4 production by IFN-gamma and IL-2 in malignant T cells may be one of the important parameters to be assessed in the design of anticancer-specific immunotherapy. In summary, we report that malignant T cells produce IL-4, a type 2 cytokine (Th2 cell response) that acts as a growth factor and which may play a critical role in PTCL disease mechanism.

Aged↗
PubMed1998

Divergent cytokine production profile in Behçet's disease. Altered Th1/Th2 cell cytokine pattern.

OBJECTIVE: To determine Th1/Th2 cell response cytokine production profile in Behçet's disease (BD). METHODS: Interleukin 2 (IL-2), interferon-gamma (IFN-gamma) and IL-12 (Th1 cell response), and IL-4, IL-10, and IL-13 (Th2 cell response) cytokine production from anti-CD3/anti-CD40 stimulated peripheral blood mononuclear cells (PBMC) were measured by ELISA. RESULTS: PBMC from patients with BD produced higher levels of IL-4, IL-10, and IL-13 (Th2 cell response), almost normal levels of IL-2 (Th1 cell response), but highly deficient IFN-gamma and IL-12 (Th1 cell response). The additions of exogenous recombinant IFN-gamma to the anti-CD3 stimulated PBMC dramatically changed this pattern with enhanced IL-12 and concomitantly decreased IL-4 and IL-10 production. CONCLUSION: The immune system in BD may be characterized by a divergent cytokine production profile of mixed Th1/Th2 (Th0) cell type; IFN-gamma is critical in modulating the IL-4, IL-10, and IL-12 cytokine network pathway in this disease.

Adult↗
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↗
PubMed1996

CD4+ T cell inducible immunoregulatory cytokine response in rheumatoid arthritis.

OBJECTIVE: Monocytes and CD4+/CD8+ T cells produce immunoregulatory cytokines that participate in the pathogenesis of various immune disorders. We investigated the secretion of Th1-Th2 cell response cytokine production of CD4+/CD8+ T cells from the synovial fluid (SF) and blood of patients with rheumatoid arthritis (RA). METHODS: Blood and SF purified monocytes, CD4+ and CD8+ T cells were stimulated with bacterial lipopolysaccharides or anti-CD3 antibody, and secretion of various cytokines was determined by bioassay or ELISA: RESULTS: Monocytes from SF and blood of patients with RA produced highly elevated levels of interleukin-1 alpha (IL-1 alpha), IL-6, tumor necrosis factor-alpha (TNF-alpha), and granulocyte macrophage colony stimulating factor (GMCSF), the leading mediators of inflammation. However, CD4+ T cells secreted deficient levels of IL-2 and interferon-gamma (IFN-gamma), but higher levels of IL-4 and IL-10, the typical immunoregulatory Th2 cell response cytokines. CD8+ T cells also produce elevated levels of IL-4 and IL-10 but almost normal levels of IFN-gamma in this disease. CONCLUSION: The cytokine produced by monocytes (IL-alpha, IL-6, TNF-alpha, and GMCSF) and by CD4+ T cells Th2 cell responses (IL-4 and IL-10) may exert immunopathologic and immunoregulatory effects in SF and thus mediate some of the clinical manifestations of RA.

Adult↗
PubMed1995

Interleukin-8 and granulocyte-macrophage colony-stimulating factor secretion in hepatocellular carcinoma and viral chronic active hepatitis.

Interleukin-8 (IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are important mediators of inflammation and immune response in human disease. To demonstrate their importance in pathophysiological processes in liver disease, we measured the circulating levels of IL-8 and GM-CSF in patients with hepatocellular carcinoma (HCC) and chronic active hepatitis (CAH). IL-8 and GM-CSF levels in serum samples were determined with highly specific and sensitive enzyme-linked immunosorbent assays. IL-8 levels were more elevated in serum samples of patients with HCC and CAH associated with hepatitis C virus infection than HCC and CAH associated with hepatitis B virus infection. However, in all patients with autoimmune CAH and in some patients with HCC and CAH, GM-CSF levels were elevated over the baseline levels measured in all of the normals, but this difference was not statistically significant for any group. We conclude that IL-8 and GM-CSF are increased in some patients with liver diseases, and as such they may play a significant role in host defense and disease.

Carcinoma, Hepatocellular↗
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↗
PubMed1994

Peripheral T-cell lymphomas. Immunoregulatory cytokine (interleukin-2, interleukin-4, and interferon-gamma) abnormalities and autologous mixed lymphocyte reaction.

BACKGROUND: Cytokines are the most important secretions of the immune system and have a wide range of immunoregulatory functions in various immune disorders and T-cell malignancy. The authors have determined that characteristic enhanced autologous mixed lymphocyte reaction (AMLR) of the lymph node-derived malignant T-cells from peripheral T-cell lymphomas is a function of the T-cell derived cytokines interleukin (IL)-2, IL-4, and interferon-gamma (IFN-tau). METHODS: Autologous mixed lymphocyte reaction assay was performed by the standard proliferative response (3H-thymidine incorporation), by culturing autologous lymph node-derived or blood-purified T-cells with autologous blood-purified mitomycin-c treated non-T-cells. The production of IL-2, IL-4, and IFN-tau in the AMLR cultures was determined by bioassay or enzyme immunoassays. RESULTS: Enhanced IL-2 and IFN-tau but deficient IL-4 production is the most characteristic and unique feature of the augmented AMLR in peripheral T-cell lymphomas. CONCLUSION: The immunoregulatory aberrations in lymph node-derived malignant T-cells that produce highly elevated IL-2 and IFN-tau but decreased IL-4 during augmented AMLR may play an important role in immune dysfunction in this neoplasm (peripheral T-cell lymphomas).

Aged↗
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

Tumor necrosis factor alpha production in schistosomiasis with carcinoma of urinary bladder.

Schistosomiasis parasitic infection (Schistosoma haematobium) is associated in some patients with bladder cancer. The production of cytokines such as tumor necrosis factor alpha (TNF alpha) is a key event of inflammation in human infectious disease and malignancy. TNF alpha has not been previously investigated from schistosomiasis infection and bladder malignancy. In this report we demonstrate that serum levels of TNF alpha are highly elevated in patients with schistosomiasis of urinary bladder (SB), schistosomiasis with carcinoma of urinary bladder (SCB), and carcinoma of urinary bladder without schistosomiasis (CB). Purified monocytes from bladder malignancy (SCB and CB) cultured without exogenous stimuli release TNF alpha in the culture supernatants. However, lipopolysaccharides and concanavalin A stimulation of monocytes from these patients produced highly elevated levels of TNF alpha compared with normal controls. The findings that monocytes are the potent producers of TNF alpha in this malignancy may be a key observation implicating these cells in the pathophysiology of this disease. Furthermore, it was shown that serum TNF alpha levels correlated with the clinical staging of disease in both SCB and CB, with higher levels in T3 and T4 advanced-stage patients and low levels in T1 and T2 early-stage patients. These results suggest that monocyte abnormality and serum TNF alpha levels might be one of the factors contributing to the progression of 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↗