scholarly journals Immunoregulatory biological response modifiers: effect of cytokines on septic shock

1993 ◽  
Vol 2 (7) ◽  
pp. S5-S10 ◽  
Author(s):  
Michael A. Chirigos ◽  
Claudio De Simone
Keyword(s):  
Septic Shock ◽  
Immune System ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Biological Response ◽  
Therapeutic Benefit ◽  
Biological Response Modifiers ◽  
Beneficial Effects ◽  
Cellular Components ◽  
Necrosis Factor

Whole bacteria or bacterial components or their extracts were employed to restore or augment the immune system. Beneficial effects were attained with these agents in treating various diseases. These agents were named biological response modifiers (BRMs) because they regulated certain cellular components of the immune system. The cellular regulation induced by these BRMs was found to be due to cytokines. The cytokines were shown to act directly on the various cellular components and to provide therapeutic benefit in various autoimmune and immune deficiency diseases. Overproduction of specific cytokines however leads to a deleterious effect on the host. Overproduction of tumour necrosis factor (endotoxin, lipopolysaccharide) leads to septic shock. Bacteraemia is the leading cause of overproduction of tumour necrosis factor (TNF). Septic shock in many cases leads to death. Several monoclonal antibodies to lipopolysaccharide (LPS) and anticytokines have demonstrated protection against septic shock.

scholarly journals Interleukin-1, Tumour Necrosis Factor and Treatment of the Septic Shock Syndrome

1992 ◽  
Vol 3 (suppl b) ◽  
pp. 11-19
Author(s):  
Charles A Dinarello
Keyword(s):  
Septic Shock ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Neutralizing Antibodies ◽  
Inflammatory Diseases ◽  
Leukocyte Adhesion ◽  
Interleukin 1 ◽  
Platelet Activating Factor ◽  
Surface Receptors ◽  
Necrosis Factor

Treating the septic shock syndrome with antibodies that block only endotoxin has its limitations. Other targets for treating septic shock include neutralizing antibodies to the complement fragment C5a, platelet activating factor antagonists and blockade of endothelial cell leukocyte adhesion molecules. Specific blockade of the pro-inflammatory cytokines interleukin-1 (IL-1) or tumour necrosis factor (TNF) reduces the morbidity and mortality associated with septic shock. Moreover, blocking IL-1 and TNF likely has uses in treating diseases other than septic shock. Use of neutralizing antibodies to TNF or IL-1 receptors has reduced the consequences of infection and inflammation, including lethal outcomes in animal models. The IL-1 receptor antagonist, a naturally occurring cytokine, blocks shock and death due to Escherichia coli as well as ameliorates a variety of inflammatory diseases. Soluble TNF and IL-1 surface receptors, which bind their respective cytokines. also ameliorate disease processes. Clinical trials are presently evaluating the safety and efficacy of anticytokine therapies either alone or in combination.

scholarly journals TWEAK and its receptor Fn14 in the synovium of patients with rheumatoid arthritis compared to psoriatic arthritis and its response to tumour necrosis factor blockade

2009 ◽  
Vol 69 (01) ◽  
pp. 301-304 ◽  
Author(s):  
A W R van Kuijk ◽  
C A Wijbrandts ◽  
M Vinkenoog ◽  
T S Zheng ◽  
K A Reedquist ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Therapeutic Benefit ◽  
Infliximab Treatment ◽  
Before And After ◽  
Separate Cohort ◽  
Necrosis Factor ◽  
Fibroblast Like Synoviocytes

Objective:To investigate the expression of tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor inducible 14 (Fn14) in the inflamed synovium of patients with arthritis, as TWEAK blockade has been observed to have a beneficial effect in an animal model of rheumatoid arthritis (RA).Methods:Synovial tissue (ST) biopsies were obtained from 6 early, methotrexate-naive patients with RA as well as 13 patients with RA and 16 patients with psoriatic arthritis (PsA) who were matched for treatment and disease duration. Serial ST samples were obtained from a separate cohort of 13 patients with RA before and after infliximab treatment. TWEAK and Fn14 expression was evaluated by immunohistochemistry and digital image analysis.Results:TWEAK and Fn14 were clearly expressed in ST of patients with RA and PsA. TWEAK expression was significantly higher in RA (sub)lining samples compared to PsA (p = 0.005 and p = 0.014, respectively), but Fn14 expression was comparable. Double immunofluorescence showed TWEAK and Fn14 expression on fibroblast-like synoviocytes and macrophages, but not T cells. Of interest, persistent TWEAK and Fn14 expression was found after anti-TNF therapy.Conclusions:TWEAK and Fn14 are abundantly expressed in the inflamed synovium of patients with RA and PsA. This raises the possibility that blocking TWEAK/Fn14 signalling could be of therapeutic benefit in inflammatory arthritis.

Response of tumour necrosis factor-α to delayed in vitro monocyte stimulation in patients with septic shock is related to outcome

2002 ◽  
Vol 102 (3) ◽  
pp. 315-320 ◽  
Author(s):  
Olivier APPOLONI ◽  
Jean-Louis VINCENT ◽  
Jean DUCHATEAU
Keyword(s):  
Septic Shock ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
High Dose ◽  
Tumour Necrosis Factor Α ◽  
Cell Stimulation ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

We hypothesized that cytokine production following delayed in vitro cell stimulation (to reproduce physiological cellular status at baseline) may be related to outcome in patients with septic shock. A total of 20 patients were included in a prospective clinical study, conducted in a medico-surgical intensive care unit in a university hospital. Blood samples were obtained at the onset of septic shock; these were treated to retain the cells, but to wash out autologous plasma (containing potential inflammatory stimuli such as cytokines, bacterial products and drugs) and replace it with foetal calf serum. Each treated sample was divided into two sets of four aliquots, to be stimulated either immediately or after an overnight period of resting incubation at 37°C. The rest period was to allow recovery from potentially reversible endogenous or pharmacologically induced alterations in cellular response, in order to reproduce a near physiological state at baseline. In vitro cellular challenges used low-dose (0.2ng/ml) or high-dose (1ng/ml) CD14-dependent lipopolysaccharide and CD14-independent pokeweed mitogen to induce the production of tumour necrosis factor-α (TNF-α), and interleukins-1β and -10. Levels of TNF-α, interleukin-1β and interleukin-10 were significantly higher (P < 0.05) when cell stimulation was delayed for 16h, indicating a functional down-regulation of cells during septic shock. Moreover, TNF-α responses obtained with high-dose lipopolysaccharide were significantly greater in cells from patients who subsequently survived septic shock (n = 13; median value 1392pg/ml; range 592-2048pg/ml) than in cells from non-survivors (n = 7; median value 708 pg/ml; range 520-1344pg/ml). These observations support the existence of individual differences in the inflammatory response that could influence patient outcome following septic shock.

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