Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokines are important protein mediators in inflammatory joint diseases. The synovial fluid and plasma concentrations of interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-alpha), interferon-alpha (IF-alpha) and interferon-gamma (IF-gamma) were measured by RIA and ELISA in 28 rheumatoid arthritis (RA) patients (5 males and 23 females). Ten patients with knee effusions due to other causes (osteoarthritis, psoriasis, gout, rheumatic fever, systemic lupus erythematosus) were also studied. Eight of the RA patients had erosive disease. The synovial fluid IL-1 alpha and IL-2 concentrations were higher in Group 1 (erosive) [IL-1 alpha: 524 pg/ml (SEM: 127), IL-2: 3.28 ng/ml (SEM: 1.0)] than in either Group 2 (non-erosive) [IL-1 alpha: 241 pg/ml (SEM: 24), IL-2: 1.93 ng/ml (SEM: 0.6)] or Group 3 (non-RA) [IL-1 alpha: 267 pg/ml (SEM: 58), IL-2: 0.35 ng/ml (SEM: 0.6)] (p < 0.003 and p < 0.06 respectively). Plasma IL-1 and IL-2 levels were higher in Group 1 [IL-1 alpha: 408 pg/ml (SEM: 107), IL-2: 4.20 ng/ml (SEM: 1.5)] than in Group 2 [IL-1 alpha 150 pg/ml (SEM: 15), IL-2: 2.58 ng/ml (SEM: 0.7)] or Group 3 [IL-1 alpha: 140 pg/ml (SEM: 11), IL-2: 1.93 ng/ml (SEM: 0.3)] (p < 0.01, p < 0.009 respectively). There were no differences in the IFN-alpha, IFN-gamma or TNF-alpha levels between groups. These findings suggest that plasma cytokines levels may reflect synovial levels and that IL-1 alpha may play a significant role in erosive joint disease.
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PMID:Cytokine concentrations in the synovial fluid and plasma of rheumatoid arthritis patients: correlation with bony erosions. 816 43

A cell line, designated SEM, was established from the peripheral blood of a 5-year-old girl in relapse with acute lymphoblastic leukaemia (ALL). Both the lymphoblasts of the patient and the cells of the cell line SEM showed the t(4;11) chromosomal rearrangement. The analysis of the immunophenotype of the SEM cell line revealed the B-cell differentiation antigens CD19, CD22 and CDw75 in the absence of CD20, CD24 and immunoglobulin expression. Besides B-lineage antigens, SEM cells were positive for the myeloid antigens CD13, CD15, CD33 and CDw65. Immunogenotypic analysis of SEM cells showed a monoclonal rearrangement of immunoglobulin heavy-chain (IgH). T-cell receptor (TCR) gamma and delta genes. Addition of interleukin (IL)-7 promoted the growth of the patient's lymphoblasts in culture and enhanced the proliferation of SEM cells. The SEM cells also express messenger RNA (mRNA) for the IL-7 receptor (IL-7R), but no evidence for autocrine production of IL-7 by the cell line was found. Addition of IL-4, tumour necrosis factor (TNF)-alpha, interferon (IFN)-alpha, or IFN-gamma resulted in a profound inhibition of SEM growth. Thus, these cytokines may have important growth regulatory activities for biphenotypic leukaemic ALL cells.
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PMID:The acute lymphoblastic leukaemia cell line SEM with t(4;11) chromosomal rearrangement is biphenotypic and responsive to interleukin-7. 819 15

The mechanisms contributing to persistent T cell activation and poor response to glucocorticoids in chronic inflammatory illnesses such as steroid resistant (SR) asthma are poorly defined. We examined the possibility that certain cytokines, specifically IL-2 and IL-4, could affect T cell response to glucocorticoids. A [3H]dexamethasone radioligand-binding assay was used to measure the number of glucocorticoid receptors (GR) and dissociation constant (Kd) in PBMC from normal donors and patients with SR asthma, cultured in the absence and presence of these cytokines. PBMC from normal donors incubated for 48 h in the presence of combination IL-2 + IL-4 had nuclear GR with significantly reduced binding affinity (GR Kd = 36.1 +/- 1.63 nM, mean +/- SEM; p = 0.0001) as compared with PBMC incubated with medium alone (GR Kd = 6.74 +/- 0.46 nM). The cytosolic GR Kd remained unchanged. However, when PBMC were incubated with IL-2 alone or IL-4 alone, no change in GR-binding affinity was observed. Furthermore, when T cells and non-T cells were individually stimulated with combination IL-2 + IL-4, a significant reduction in GR-binding affinity was observed only in the T cell population (p = 0.0001). The IL-2 + IL-4-induced alteration in PBMC GR Kd was associated with an increase in GR number (8348 +/- 964 vs 1710 +/- 228 sites/cell; p = 0.0003). More importantly, the alteration in PBMC GR-binding affinity with IL-2 + IL-4 was associated with a functional change in T cell response to methylprednisolone MPN, i.e., a reduced inhibitory effect of MPN on PMA/ionomycin-induced T cell proliferation. These effects of IL-2 + IL-4 on PBMC GR affinity and response to MPN were blocked by co-incubation with IFN-gamma. Freshly isolated PBMC from four patients with SR asthma had a significantly reduced GR-binding affinity (Kd = 40.0 +/- 2.68 nM; p = 0.0001) when compared with seven normal subjects (7.15 +/- 0.41 nM). The altered PBMC GR binding from patients with SR asthma reversed to normal when incubated with medium alone, but was sustained with IL-2 + IL-4. These observations suggest that with persistent inflammation certain cytokines may contribute to an impaired response to glucocorticoids. Furthermore, the effects of IL-2 and IL-4 were blocked by IFN-gamma.
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PMID:Combination IL-2 and IL-4 reduces glucocorticoid receptor-binding affinity and T cell response to glucocorticoids. 837 86

Activated human monocytes and macrophages are involved in host defense against neoplastic cells. In view of cellular adoptive immunotherapy, we have studied the role of tumor necrosis factor-alpha (TNF-alpha) and gamma-interferon (IFN-gamma) in monocyte-mediated cytotoxicity on the level of both effector and leukemic target cells. Highly purified and IFN-gamma-activated monocytes were cytolytic to U937 cells up to 81.9 +/- 5.3% (mean +/- SEM) in a 24-hour MTT cytotoxicity assay at an effector-to-target-cell ratio of 10. Upon IFN-gamma activation these monocytes showed a 20-fold increase in TNF-alpha secretion of 663 +/- 122 pg/mL. Comparable concentrations of recombinant human TNF-alpha showed only cytostatic effects on U937 cells of approximately 20% after 24 hours, similar to the cytostatic effects of IFN-gamma-activated monocyte culture supernatants. These effects could be fully reversed by anti-TNF-alpha antibodies. U937 cells pretreated with TNF-alpha were almost completely resistant to monocyte-mediated cytotoxicity, supernatant-mediated cytostasis and to TNF-alpha up to 10(4) U/mL. IFN-gamma-activated monocytes were able to lyse TNF-alpha-modified U937 cells whereas IFN-gamma-activated monocyte supernatants showed only cytostatic activity after prolonged incubation. Additionally, target cell modulation by IFN-gamma potentiated the TNF-alpha-dependent cytolytic and cytostatic effects of monocytes, monocyte culture supernatants and TNF-alpha. We conclude that monocytes as a cellular component in monocyte-mediated cytotoxicity are far more potent in lysis of leukemic target cells than are secreted monokines. Furthermore, IFN-gamma and TNF-alpha are involved in the regulation of the susceptibility of leukemic cells for lysis by interactions with monocytes.
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PMID:Cellular and cytokine dependent monocyte-mediated leukemic cell death: modulation by interferon-gamma and tumor necrosis factor-alpha. 844 Mar 44

Glucocorticosteroids (GCS) are beneficial in allergic asthma. GCS therapy results in reduced mRNA expression of interleukin-4 (IL-4) and IL-5 in cells from bronchoalveolar lavage (BAL) but not of IFN-gamma. In vitro studies with blood-derived T cells, however, show inhibition of all three cytokines by GCS. We studied the effects of GCS on T cells from BAL in vitro, namely Th0-, Th1, and Th2-like clones; and we compared BAL- with blood-derived clones. Dexamethasone (DEX) inhibited the anti-CD3-induced production of IL-4, IL-5 and IFN-gamma in all 20 clones tested. IFN-gamma production was inhibited significantly less than IL-4 and IL-5. DEX enhanced the ratio IFN-gamma/IL-4 (mean +/- SEM: control, 28.7 +/- 17.6; with 10-7 M DEX, 55.0 +/- 27.5, P<0.005). Interestingly, two categories of clones were distinguished based on the effects of GCS on IL-2 production and IL-2R alpha expression and proliferation; 1) In low IL-2 producers DEX blocked IL-2 production and decreased IL-2R alpha expression and proliferation; 2) In high IL-2 producers DEX inhibited IL-2 production partially and enhanced IL-2R alpha expression and proliferation. Anti-IL-2 and anti-IL2R alpha blocked the DEX-induced increase in proliferation. High levels of added IL-2 induced the second type of response. In conclusion, the production of IL-4 and IL-5 by T-cell clones (derived either from BAL or blood) was more sensitive to inhibition by DEX than that of IFN-gamma, which may account for the therapeutic effects of glucocorticosteroids in patients with asthma. The differential effects of DEX on the proliferation of high and low IL-2 producers in vitro may implicate a selective outgrowth of Th1-like T cells in vivo in patients treated with steroids.
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PMID:Glucocorticosteroids affect functions of airway- and blood-derived human T-cell clones, favoring the Th1 profile through two mechanisms. 860 Sep 44

Calcium-dependent signal transduction is essential to the induction of cytokine expression by stimuli acting through the T cell receptor. In vitro, the immunosuppressant cyclosporine (CyA) blocks this pathway by inhibition of calcineurin (CN) phosphatase activity. But in vivo, patients on CyA have only 50% inhibition of CN and can mount cytokine responses. To simulate this state of partial inhibition, we studied the responses of human peripheral blood mononuclear leucocytes (PBL) in vitro at low CyA concentrations. PBL were challenged in vitro with calcium ionophores or anti-CD3 monoclonal antibody. The induction of IFN-gamma (interferon-gamma) and IL-2 (interleukin 2) steady-state mRNA was studied by Northern blotting and reverse transcriptase-polymerase chain reaction. IFN-gamma was assessed in a radiolabelled antibody binding assay or by ELISA (enzyme-linked immunosorbent assay). CN was assessed by dephosphorylation of a 32P-serine labelled 19 amino acid substrate. CyA inhibited CN with an IC50 (concentration giving 50% inhibition) of 10 ng/ml (95% confidence interval, CI = 8-13 ng/ml). Likewise, the induction of IFN-gamma and IL-2 mRNA by calcium ionophore A23187 was inhibited with IC50 of 14 ng/ml (95% CI = 8-27 ng/ml) and 32 ng/ml (95% CI = 5-178 ng/ml), respectively, while the IC50 for inhibition of IFN-gamma protein secretion was 8 ng/ml (95% CI = 9-18 ng/ml). Partial inhibition of CN also altered the threshold for IFN-gamma induction. CyA 10 ng/ml inhibited IFN-gamma induction by anti-CD3 monoclonal antibody OKT3 significantly more at low OKT3 concentrations (10 ng/ml, mean +/- SEM = 72 +/- 9% inhibition) compared to high OKT3 concentrations (1000 ng/ml, 47 +/- 6%, p < 0.01). Similar results were seen using high and low concentrations of A23187. Finally, cells pretreated with CyA recovered the ability to respond to high concentrations of A23187 (5 microM) faster than low concentrations (0.5 microM). We conclude that the principal defect in lymphocytes with partial CN inhibition is a reduction in maximum cytokine output which is closely related to the degree of CN inhibition. In addition, there is significantly greater inhibition of weak stimuli compared to maximal stimuli. These defects may explain why patients on CyA can have a reduction in immune responsiveness but still retain protection from infection.
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PMID:The functional consequences of partial calcineurin inhibition in human peripheral blood mononuclear leucocytes. 876 5

IFN-gamma is a potent pro-inflammatory cytokine involved in the immunologic rejection of transplanted organs. Having previously demonstrated differential suppressive effects of methylprednisolone (MP), prednisolone (P) and cyclosporine (CsA) on dialysis patients' lymphocyte proliferative responses to phytohaemagglutinin (PHA), we studied the effects of these drugs on dialysis patients' lymphocyte IFN-gamma production during mitogenic and allogeneic (MLR) stimulation. The mean +/- SEM 50% inhibitory concentration (ng/ml) on cell proliferation was significantly lower for MP than P in PHA-stimulated haemodialysis (HD) patients' (35 +/- 7 vs 152 +/- 25, P < 0.001) and peritoneal dialysis (PD) patients' (35 +/- 11 vs 134 +/- 33, P = 0.001) cultures and in HD patients' MLR cultures (15 +/- 3 vs 48 +/- 9, P < 0.001). The mean +/- SEM fractional responses (PHA or MLR + drug/PHA or MLR) in culture supernatant IFN-gamma concentrations were significantly lower with 10(-7) M concentrations of MP than P in HD (0.19 +/- 0.05 vs 0.31 +/- 0.06, P = 0.01) and PD (0.30 +/- 0.11 vs 0.46 +/- 0.11, P < 0.05) PHA cultures and in HD MLR cultures (0.15 +/- 0.04 vs 0.28 +/- 0.07, P = 0.01). CsA (400 ng/ml) alone not only caused less than 50% inhibition of IFN-gamma production in 15/27 HD PHA, 6/14 PD PHA and 4/13 HD MLR cultures, but actually stimulated it in 9 HD and 5 PD PHA cultures. The results suggest that: (1) MP has greater immunosuppressive potential than P for renal transplant recipients; (2) the stimulation of IFN-gamma by CsA in some patients could be harmful in patients with initial allograft dysfunction; and (3) pre-transplant in-vitro assessment of recipients' PBMC responsiveness to glucocorticoids and CsA may help individualize the post-transplant immunosuppressive regimen.
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PMID:Differential suppression of dialysis patients' lymphocyte IFN-gamma production by glucocorticoids and cyclosporine. 898 Aug 83

We have compared an immunocytochemical and a flow cytofluorimetric method to detect intracellular IFN-gamma, IL-4 and IL-5 in T-cell clones, peripheral blood mononuclear cells (PBMC) and bronchoalveolar lavage fluid (BALF) cells. Intracellular bound cytokine-specific antibodies were visualized either with amino-ethyl carbazole (for immunocytochemistry), or with fluorescent antibodies (for flow cytofluorimetry). The staining was inhibited with recombinant cytokines and corresponded qualitatively and quantitatively to cytokine levels in the supernatants of T-helper-0 (Th0), Th1 and Th2 clones. In analysing in vitro stimulated cells, sufficient signal in the fluorimetric assay was only obtained after the addition of monensin to the cultures. We then observed a good correlation between immunocytochemical (with no monensin added) and the flow cytofluorimetric staining for all three cytokines (PBMC, IFN-gamma and IL-4, rho = 0.9, no IL-5 detectable; clones, IL-5, rho = 0.81, all three p < 0.05). However, compared to flow cytometry, a greater percentage of positively stained cells was frequently observed using immunocytochemistry. In BALF cells, the immunocytochemical method was able to detect significant percentages of positive cells without in vitro stimulation of the cells, in contrast to the flow cytofluorimetric method. In BALF cells from sarcoidosis patients, T-cells were mainly IFN-gamma-positive (immunocytochemically assessed), both with (mean +/- SEM, 39.7 +/- 9.8%), and without (3.5 +/- 1.3%) in vitro stimulation. In BALF cells from allergic subjects, the immunocytochemical method showed lymphocytes positive for IFN-gamma (40.3 +/- 8.3%), IL-4 (19.1 +/- 0.49) and IL-5 (6.1 +/- 3.1). We conclude that both methods can be used to assess the production of IFN-gamma, IL-4 or IL-5 at the single-cell level in T-cell clones, PBMC and cells from the BALF. The high sensitivity and the low number of cells required for the immunocytochemical method indicate that this method can provide detailed information on cytokine production of airway-derived cells in diseases with airway inflammation such as sarcoidosis and asthma.
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PMID:Immunocytochemical and flow cytofluorimetric detection of intracellular IL-4, IL-5 and IFN-gamma: applications using blood- and airway-derived cells. 913 33

We evaluated the levels of inositolmono-(IP1), di(IP2), tri-(IP3) and tetraphosphates (IP4) in human neutrophils (N) stimulated with gamma interferon (IFN-gamma) (200 microliters from a pool of cell culture supernatant obtained from 1 x 10(7) PHA-primed peripheral blood mononuclear cells (30-60 min at 37 degrees C, 5% CO2)) in the presence of in the absence of interleukin 10 (IL-10) (10 micrograms/10 microliters). The results, reported as mean +/- SEM cpm, showed that IFN-gamma induced a significant increase only in the IP3 level (N + medium = 1,413 +/- 172 and N + IFN-gamma = 8,875 +/- 832). However, this activation mediated by IFN-gamma was blocked partially in the presence of IL-10 (N + IFN-gamma + IL-10 = 2,430 +/- 239) (P < 0.05). Interleukin 10 alone did not induce significant alterations in the content of IP1 (1,203 +/- 123), IP2 (1,880 +/- 163), IP3 (938 +/- 102) or IP4 (2,403 +/- 345) when compared to the respective controls in the absence of IL-10 (IP1 = 1,625 +/- 132; IP2 = 1,343 +/- 149; P3 = 1,413 +/- 172 and IP4 = 3,281 +/- 234). We also demonstrated the inhibitory effect of IL-10 of chemoluminescence generation by human neutrophils during phagocytosis of opsonized particles (OZ). Chemoluminescence generation was enhanced by IFN-gamma (N = OZ = 42.8 +/- 3.9 and N + OZ + IFN-gamma = 66.5 +/- 4.3) and this effect was reduced by IL-10 (N + OZ + IFN-gamma + IL-10 = 37.6 +/- 5.1). These data suggest that IL-10 modulates the neutrophil response and may be important for the development of new treatments of inflammatory injury.
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PMID:Effect of gamma interferon and interleukin 10 on phosphoinositol turnover by human neutrophils in vitro. 918 Nov 14

Human peripheral blood cells, especially lymphocytes and thrombocytes, are extensively studied in neuropsychiatric research both as tools for investigating systemic derangements in neuropsychiatric disorders, and as peripheral models for getting information on central nervous system biochemistry. Specific interferon (IFN)-gamma receptors have been found on both human lymphocytes and neural cells. The aim of the present study has been to evaluate IFN-gamma binding on peripheral blood T lymphocytes from parkinsonian patients, as compared with that on blood T cells from healthy subjects. We have found that T lymphocytes from parkinsonian patients bear a significantly smaller amount of IFN-gamma receptors than those from controls. Such IFN-gamma binding sites are of the same type in patients and healthy subjects (Kd (mean +/- SEM): 1.4 +/- 0.07 vs. 1.2 +/- 0.06, respectively). These findings, which are not specific for Parkinson's disease, are discussed in terms of its immunopathogenesis, since it has been reported that activated T lymphocytes have decreased amounts of IFN-gamma receptors.
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PMID:T-lymphocyte immuno-interferon binding in parkinsonian patients. 920 82


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