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J Steinhoff - One of the best experts on this subject based on the ideXlab platform.
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production of Monokines in patients under polysulphone haemodiafiltration is influenced by the ultrafiltration flow rate
Nephrology Dialysis Transplantation, 2001Co-Authors: Michael Mullersteinhardt, Norman Kock, Christoph Hartel, H Kirchner, J SteinhoffAbstract:BACKGROUND: Chronic haemodialysis patients show various clinical signs of immunodeficiency and there is growing evidence that a dysregulated monocyte cytokine production is heavily involved in this deficiency. The production of Monokines in vitro has been proposed to correlate closely with the in vivo immune status and to be of high clinical relevance in cuprophane haemodialysis. Even though it is well known that the biocompatibility of dialyser membranes has a significant impact on immune functions, little is known about the influence of the ultrafiltration flow rate (UFR). The aim of this study was to investigate the potential long-term effects of UFR on the production of interleukin-10 (IL-10), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in an intra-individual study design. METHODS: In 11 patients previously treated with polysulphone haemodiafiltration, UFR was reduced from 40-46 ml/min to 24-28 ml/min, then to 7-10 ml/min before it was reinstated at 40-46 ml/min for periods of 4 weeks each. Monokine secretion into culture supernatants and mRNA expression (assessed using a novel Taqman PCR technique), were determined in a whole blood assay after lipopolysaccharide stimulation. RESULTS: Reduction of UFR led to a significant increase in IL-10 secretion and mRNA expression (P=0.012, P=0.001). Conversely, a substantial (but not complete) decrease was observed when UFR returned to initial levels. In contrast, supernatant concentrations of IL-1beta (P=0.04) and IL-6 (P=0.003), and mRNA expression of both Monokines (P<0.001, P<0.001) decreased significantly when UFR was reduced. Calculation of the IL-1beta/IL-10 ratio also revealed a decrease when UFR was reduced, with an increase again being observed when the initial degree of UFR was reinstated (P<0.001). CONCLUSIONS: These results indicate a significant impact of UFR on the production of Monokines at both the transcriptional and the protein level. We suggest that middle molecule removal has to be considered as a possible pathophysiological mechanism to explain our findings. Since Monokine production in vitro was shown to be closely correlated with the in vivo immune status in patients on cuprophane haemodialysis, further investigations are necessary to clarify the impact of UFR on the immunocompetence of patients under polysulphone haemodiafiltration.
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Production of Monokines in patients under polysulphone haemodiafiltration is influenced by the ultrafiltration flow rate
Nephrology dialysis transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2001Co-Authors: Michael Müller-steinhardt, Norman Kock, Christoph Hartel, H Kirchner, J SteinhoffAbstract:Background. Chronic haemodialysis patients show various clinical signs of immunodeficiency and there is growing evidence that a dysregulated monocyte cytokine production is heavily involved in this deficiency. The production of Monokines in vitro has been proposed to correlate closely with the in vivo immune status and to be of high clinical relevance in cuprophane haemodialysis. Even though it is well known that the biocompatibility of dialyser membranes has a significant impact on immune functions, little is known about the influence of the ultrafiltration flow rate (UFR). The aim of this study was to investigate the potential long-term effects of UFR on the production of interleukin-10 (IL-10), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in an intra-individual study design. Methods. In 11 patients previously treated with polysulphone haemodiafiltration, UFR was reduced from 40-46 ml min to 24-28 ml/min, then to 7-10 ml/min before it was reinstated at 40-46 ml min for periods of 4 weeks each. Monokine secretion into culture supernatants and mRNA expression (assessed using a novel Taqman PCR technique), were determined in a whole blood assay after lipopolysaccharide stimulation. Results. Reduction of UFR led to a significant increase in IL-10 secretion and mRNA expression (P = 0.012, P=0.001). Conversely, a substantial (but not complete) decrease was observed when UFR returned to initial levels. In contrast, supernatant concentrations of IL-1β (P=0.04) and IL-6 (P = 0.003), and mRNA expression of both Monokines (P < 0.001, P < 0.001) decreased significantly when UFR was reduced. Calculation of the IL-1β/IL-10 ratio also revealed a decrease when UFR was reduced, with an increase again being observed when the initial degree of UFR was reinstated (P < 0.001). Conclusions. These results indicate a significant impact of UFR on the production of Monokines at both the transcriptional and the protein level. We suggest that middle molecule removal has to be considered as a possible pathophysiological mechanism to explain our findings. Since Monokine production in vitro was shown to be closely correlated with the in vivo immune status in patients on cuprophane haemodialysis, further investigations are necessary to clarify the impact of UFR on the immunocompetence of patients under polysulphone haemodiafiltration.
Shaun R Mccoll - One of the best experts on this subject based on the ideXlab platform.
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synergistic effect of interleukin 1β and tumor necrosis factor α on interleukin 8 gene expression in synovial fibroblasts evidence that interleukin 8 is the major neutrophil activating chemokine released in response to Monokine activation
Arthritis & Rheumatism, 1993Co-Authors: Palaniswami Rathanaswami, Mohamed Hachicha, Wai Lee Wong, Thomas J Schall, Shaun R MccollAbstract:OBJECTIVE To investigate both the involvement of chemokines in general and the relative importance of specific chemokines in rheumatoid arthritis (RA), we characterized the effect of the Monokines tumor necrosis factor alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) on the synthesis of neutrophil-activating factors by synovial fibroblasts isolated from the joints of patients with RA. METHODS Neutrophil-stimulating activity was assessed by determining intracellular calcium mobilization. IL-8 synthesis and secretion was assessed by specific enzyme-linked immunosorbent assay, and IL-8 messenger RNA (mRNA) levels were determined by Northern blot. RESULTS Treatment of synovial fibroblasts with IL-1 beta and TNF alpha resulted in the production of an activity which induced intracellular calcium mobilization in peripheral blood neutrophils. The 2 Monokines combined had a synergistic effect on the release of the neutrophil-stimulating activity. The effect of the 2 Monokines required gene transcription and translation, and closely mimicked the pattern of IL-8 secretion induced in these cells by the Monokines. We confirmed that the majority of the neutrophil-stimulating activity was IL-8 by 3 different approaches: cross-desensitization experiments with IL-8, melanoma growth-stimulatory activity, and neutrophil-activating peptide 2, stimulation of calcium mobilization in cells transfected with the IL-8 receptor complementary DNA, and inhibition of the activity following pretreatment of the supernatants with an anti-IL-8 antibody. TNF alpha and IL-1 beta induced a time- and dose-dependent release of immunoreactive IL-8. A synergistic effect of TNF alpha and IL-1 beta was also observed for both IL-8 production and accumulation of IL-8 mRNA. CONCLUSION These results indicate that the Monokines TNF alpha and IL-1 beta synergistically activate IL-8 expression and protein secretion by synovial fibroblasts, and that under these conditions, IL-8 appears to be the major neutrophil-activating factor released.
Philip Scuderi - One of the best experts on this subject based on the ideXlab platform.
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Serum levels of tumor necrosis factor alpha, interleukin-1 alpha and beta in healthy elderly subjects
AGE, 1991Co-Authors: Arshag D. Mooradian, Richard L. Reed, Philip ScuderiAbstract:To determine the age-related changes in Monokine secretion, the serum concentrations of tumor necrosis factor alpha (TNF), interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) were measured in 31 young healthy subjects (21–35 years old) and 19 healthy elderly subjects (65–83 years old). There were no differences between the two groups with respect to serum concentrations of these cytokines. We also measured in a subgroup of young (n=8–11) and elderly (n=8–10) subjects the in vitro secretion of TNF and IL-1β in response to adding to the medium lipopolysaccharide (LPS, 2 ng/ml), interferon gamma (50 U/ml) or advanced glycosylation endproduct of bovine serum albumin (250 ug/ml). Only LPS-stimulated IL-1β production was significantly reduced in elderly subjects (456.7 ± 229.9 vs 1118.8 ± 494.8 pg/ml). It is concluded that with the possible exception of LPS-stimulated IL-1β production, Monokine secretion measured in this study is well preserved in elderly subjects.
Takashi Horie - One of the best experts on this subject based on the ideXlab platform.
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Effects of fibronectin on the Monokine production by cultured-human monocytes
Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology, 1997Co-Authors: Susumu Nishinarita, T. Takizawa, Noboru Kitamura, Takanori Azuma, Hideo Takahashi, Takashi HorieAbstract:The effect of fibronectin (FN) on IL-1 alpha, IL-1 beta, TNF-alpha, and IL-6 production was investigated with cultured monocytes isolated from human peripheral blood. Monokine concentrations were determined by ELISA. FN markedly stimulated the secretion of IL-1 alpha, IL-1 beta, TNF-alpha, and IL-6 from cultured monocytes. Northern blot analysis revealed the up-regulated expression of mRNA specific for each Monokine on exposure of monocytes to FN. GM-CSF, IFN-gamma, and LPS synergistically enhanced FN-induced IL-1 alpha production. We further investigated the signal transduction pathways involved in FN-stimulated Monokine secretion. FN-stimulated TNF-alpha secretion was markedly inhibited by either herbimycin A or genistein, inhibitors of protein tyrosine kinase (PTK), but was not affected by staurosporin, a inhibitor of protein kinase C (PKC). The results suggest that PTK is required for FN-stimulated TNF-alpha secretion. In contrast, LPS-stimulated TNF-alpha secretion was markedly inhibited by not only herbimycin A or genistein, but also staurosporin. Therefore, both PTK and PKC may be involved in LPS-stimulated TNF-alpha secretion. We also demonstrated that, in monocytes, cytoplasmic proteins of about 70 and 240 kDa were phosphorylated after FN stimulation. Our results indicate that FN may contribute to the inflammatory response of monocyte by inducing Monokine production.
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interaction of the cell binding domain of fibronectin with vla 5 integrin induces Monokine production in cultured human monocytes
Clinical and Experimental Immunology, 1995Co-Authors: T. Takizawa, Susumu Nishinarita, Noboru Kitamura, J Hayakawa, Hoil Kang, Y. Tomita, K Mitamura, Keiji Yamagami, Takashi HorieAbstract:The effect of fibronectin on IL-1 alpha, IL-1 beta, tumour necrosis factor-alpha (TNF-alpha), and IL-6 production was investigated with cultured monocytes isolated from human peripheral blood. Monokine concentrations were determined by both ELISA and bioassay. Fibronectin markedly stimulated the secretion of IL-1 alpha, IL-1 beta, TNF-alpha and IL-6 from cultured monocytes in a dose-dependent manner, with the maximal effect apparent within 24 h. Northern blot analysis revealed a marked increase in the abundance of mRNA specific for each Monokine on exposure of monocytes to fibronectin. Monoclonal antibodies to the alpha chain of very late antigen (VLA)-5, the beta 1 integrin, the alpha chain of Mac-1, and the beta 2 integrin, as well as the synthetic peptide of GRGDSP (which corresponds to the cell-binding domain of fibronectin), inhibited (> 50%) fibronectin-induced Monokine production. Monoclonal antibodies to the alpha chain of VLA-4, and the alpha chain of LFA-1, as well as the synthetic peptide CS-1 (which corresponds to the alternatively spliced connecting segment of fibronectin) and the control peptide GRADSP, had no inhibitory effect on Monokine production. A MoAb, R60, that recognizes an epitope of the fibronectin molecule that includes the RGD sequence, inhibited Monokine production, whereas the MoAb Y16, which recognizes another epitope of fibronectin not including RGD, did not. These results indicate that fibronectin-induced production of IL-1 alpha, IL-1 beta, TNF-alpha and IL-6 from cultured monocytes is mediated predominantly by interaction of the cell-binding domain of fibronectin with VLA-5, although Mac-1 also may contribute to this effect of fibronectin. Our results indicate that the interaction of fibronectin with integrins may contribute to the cytokine network in inflammatory response.
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Interaction of the cell‐binding domain of fibronectin with VLA‐5 integrin induces Monokine production in cultured human monocytes
Clinical and experimental immunology, 1995Co-Authors: T. Takizawa, Susumu Nishinarita, Noboru Kitamura, J Hayakawa, Hoil Kang, Y. Tomita, K Mitamura, Keiji Yamagami, Takashi HorieAbstract:The effect of fibronectin on IL-1 alpha, IL-1 beta, tumour necrosis factor-alpha (TNF-alpha), and IL-6 production was investigated with cultured monocytes isolated from human peripheral blood. Monokine concentrations were determined by both ELISA and bioassay. Fibronectin markedly stimulated the secretion of IL-1 alpha, IL-1 beta, TNF-alpha and IL-6 from cultured monocytes in a dose-dependent manner, with the maximal effect apparent within 24 h. Northern blot analysis revealed a marked increase in the abundance of mRNA specific for each Monokine on exposure of monocytes to fibronectin. Monoclonal antibodies to the alpha chain of very late antigen (VLA)-5, the beta 1 integrin, the alpha chain of Mac-1, and the beta 2 integrin, as well as the synthetic peptide of GRGDSP (which corresponds to the cell-binding domain of fibronectin), inhibited (> 50%) fibronectin-induced Monokine production. Monoclonal antibodies to the alpha chain of VLA-4, and the alpha chain of LFA-1, as well as the synthetic peptide CS-1 (which corresponds to the alternatively spliced connecting segment of fibronectin) and the control peptide GRADSP, had no inhibitory effect on Monokine production. A MoAb, R60, that recognizes an epitope of the fibronectin molecule that includes the RGD sequence, inhibited Monokine production, whereas the MoAb Y16, which recognizes another epitope of fibronectin not including RGD, did not. These results indicate that fibronectin-induced production of IL-1 alpha, IL-1 beta, TNF-alpha and IL-6 from cultured monocytes is mediated predominantly by interaction of the cell-binding domain of fibronectin with VLA-5, although Mac-1 also may contribute to this effect of fibronectin. Our results indicate that the interaction of fibronectin with integrins may contribute to the cytokine network in inflammatory response.
Arshag D. Mooradian - One of the best experts on this subject based on the ideXlab platform.
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Serum levels of tumor necrosis factor alpha, interleukin-1 alpha and beta in healthy elderly subjects
AGE, 1991Co-Authors: Arshag D. Mooradian, Richard L. Reed, Philip ScuderiAbstract:To determine the age-related changes in Monokine secretion, the serum concentrations of tumor necrosis factor alpha (TNF), interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) were measured in 31 young healthy subjects (21–35 years old) and 19 healthy elderly subjects (65–83 years old). There were no differences between the two groups with respect to serum concentrations of these cytokines. We also measured in a subgroup of young (n=8–11) and elderly (n=8–10) subjects the in vitro secretion of TNF and IL-1β in response to adding to the medium lipopolysaccharide (LPS, 2 ng/ml), interferon gamma (50 U/ml) or advanced glycosylation endproduct of bovine serum albumin (250 ug/ml). Only LPS-stimulated IL-1β production was significantly reduced in elderly subjects (456.7 ± 229.9 vs 1118.8 ± 494.8 pg/ml). It is concluded that with the possible exception of LPS-stimulated IL-1β production, Monokine secretion measured in this study is well preserved in elderly subjects.