scholarly journals Pharmacological Studies on 3-Formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-one (T-614), a Novel Antiinflammatory Agent. 4th Communication: Inhibitory Effect on the Production of Interleukin-1 and Interleukin-6.

1992 ◽  
Vol 15 (11) ◽  
pp. 649-655 ◽  
Author(s):  
Keiichi TANAKA ◽  
Yukihiko AIKAWA ◽  
Hiroki KAWASAKI ◽  
Keiko ASAOKA ◽  
Takihiro INABA ◽  
...  
1991 ◽  
Vol 124 (5) ◽  
pp. 577-582 ◽  
Author(s):  
Å. Krogh Rasmussen ◽  
L. Kayser ◽  
K. Bech ◽  
U. Feldt-Rasmussen ◽  
H. Perrild ◽  
...  

Abstract. Interleukin 6 has been suggested as second mediator of the effects of interleukin 1 in some cell systems. Interleukin 1 has previously been shown to inhibit the function of human thyrocytes in secondary cultures. We have therefore studied the influence of interleukin 6 (10−1−5·107 U/l) on the function of thyroid cells. Recombinant interleukin 6 slightly inhibited the production of cAMP, but failed to influence the production of thyroglobulin or the DNA content. Endotoxins (lipopolysaccharides from Salmonella abortus equi or Yersinia enterocolitica) had only a slightly inhibitory effect on thyroid cell functions, and the effect of interleukin 6 could not by itself be explained by endotoxin contamination. The effect of interleukin 6 did not mimick effects on thyroid cells afforded by recombinant interleukin 1α and 1β. Furthermore, antibodies to interleukin 6 were not able to inhibit the interleukin 1β-induced inhibition of thyroid cell functions. In conclusion, it is unlikely that interleukin 6 by itself mediates the biological effects of interleukin 1 on human thyroid cells.


1990 ◽  
Vol 272 (1) ◽  
pp. 243-245 ◽  
Author(s):  
C Southern ◽  
D Schulster ◽  
I C Green

Glucose-induced insulin secretion from islets cultured in the presence of interleukin-6 (IL-6) for 12-24 h was inhibited to a similar extent as when islets were treated with interleukin-1 beta (IL-1 beta). However, unlike IL-1 beta, IL-6 did not potentiate insulin secretion during an acute (30 min) exposure of islets to the cytokine, nor did it inhibit DNA synthesis during a 24 h culture period. A 12 h pretreatment of islets with tumour necrosis factor-alpha (TNF-alpha) combined with IL-1 beta potentiated the inhibitory effect of IL-1 beta on secretion, such that 20 mM-glucose-induced insulin secretion was abolished. No synergistic inhibition of secretion was observed with TNF-alpha and IL-6. However, IL-1 beta and IL-6 were found to inhibit insulin secretion in an additive manner. These results suggest that IL-6 inhibits insulin secretion in a manner distinct from that of IL-1 beta, and that IL-6 is unlikely to mediate the inhibitory effects of IL-1 beta or TNF-alpha on rat islets of Langerhans.


2016 ◽  
Vol 36 (01) ◽  
pp. 49-51
Author(s):  
T. Geikowski ◽  
D. Peters ◽  
J. Peitz ◽  
G. Horneff ◽  
S. Wintrich

ZusammenfassungDie systemische juvenile idiopathische Arthritis (sJIA) und das familiäre Mittelmeerfieber (FMF) zeigen mit Fieber, Arthritis, Exanthem, generalisierter Lymphadenopathie und Sero sitis viele Gemeinsamkeiten. Therapieoptio-nen bei der sJIA sind neben Glukokortikoi-den, nichtsteroidalen Antirheumatika und Methotrexat, Biologika wie Interleukin-1-und Interleukin-6-Antagonisten. Firstline Therapie des FMF ist Colchicin. Bei Therapie resistenz oder -unverträglichkeit können aber auch bei dieser Erkrankung Interleukin-1-und Interleukin-6-Antagonisten erfolgreich eingesetzt werden.Berichtet wird über einen elf Jahre alten Jungen, geboren in Armenien. Im Alter von zwei Jahren kam es zu anhaltendem Fieber mit ausgeprägter Arthritis. Die Diagnose sJIA wurde gestellt und das Vorliegen eines FMF genetisch nachgewiesen. Unter Therapie mit Kortikosteroiden, Sulfasalazin und Colchicin entwickelte der Patient eine deutliche Dystro phie und ausgeprägte Destruktionen der Hüft-, Knie- und Sprunggelenke mit resultie-render Laufunfähigkeit. Die Halswirbelsäule war durch Ankylosen kyphotisch fixiert. La borchemisch waren die Entzündungszeichen deutlich erhöht. Röntgen- und CT-Aufnah-men zeigten das Ausmaß der Gelenkzer -störung. Nach einem Jahr unter intravenöser Tocilizumab-Therapie liegen CRP, SAA und BSG im Normbereich. Bestehende Kontraktu ren sind unter intensiver Physiotherapie rück-läufig. Der Patient ist mit eigenem Rollstuhl mobil.Bei diesem Patient liegt sowohl eine systemische JIA als auch ein familiäres Mittelmeerfieber vor. Tocilizumab ist bereits seit mehreren Jahren für die Behandlung der systemischen JIA zugelassen. Unser Patient zeigt unter Tocilizumab eine Remission beider Erkrankungen.


2009 ◽  
Vol 29 (02) ◽  
pp. 81-93 ◽  
Author(s):  
G. Horneff

ZusammenfassungDie Therapie der juvenilen idiopathischen Arthritis erfolgt durch eine Kombination von nichtsteroidalen Antirheumatika, systemischen und/oder intraartikulären Glukokortikoiden, klassischen Basistherapeutika, Immunsupressiva und Biologika. Die neuen bio-logischen Medikamente erwiesen sich als au-ßerordentlich wirksam, auch bei schweren oder bislang therapierefraktären Verläufen. Drei Tumor-Nekrose-Faktor-Inhibitoren (Eta-nercept, Adalimumab und Infliximab) wurden bereits untersucht. Weitere therapeutische Optionen bestehen durch Inhibition von Interleukin-1 durch Anakinra, Canakinumab und Rilonacept, Interleukin 6 durch Tocilizumab oder der Inhibition der T-Zellaktivierung durch Abatacept. In dieser Übersichtsarbeit werden die pharmakologischen Therapieoptionen orientierend an der Existenz von kontrollierten randomisierten Studien dargestellt.


1986 ◽  
Vol 55 (01) ◽  
pp. 012-018 ◽  
Author(s):  
Paolo Gresele ◽  
Jef Arnout ◽  
Hans Deckmyn ◽  
Jos Vermylen

SummaryDipyridamole inhibits platelet aggregation in whole blood at lower concentrations than in plasma. The blood cells responsible for increased effectiveness in blood are the erythrocytes. Using the impedance aggregometer we have carried out a series of pharmacological studies in vitro to elucidate the mechanism of action of dipyridamole in whole blood. Adenosine deaminase, an enzyme breaking down adenosine, reverses the inhibitory action of dipyridamole. Two different adenosine receptor antagonists, 5’-deoxy-5’-methylthioadenosine and theophylline, also partially neutralize the activity of dipyridamole in blood. Enprofylline, a phosphodiesterase inhibitor with almost no adenosine receptor antagonistic properties, potentiates the inhibition of platelet aggregation by dipyridamole. An inhibitory effect similar to that of dipyridamole can be obtained combining a pure adenosine uptake inhibitor (RE 102 BS) with a pure phosphodiesterase inhibitor (MX-MB 82 or enprofylline). Mixing the blood during preincubation with dipyridamole increases the degree of inhibition. Lowering the haematocrit slightly reduces the effectiveness.Although we did not carry out direct measurements of adenosine levels, the results of our pharmacological studies clearly show that dipyridamole inhibits platelet aggregation in whole blood by blocking the reuptake of adenosine formed from precursors released by red blood cells following microtrauma. Its slight phosphodiesterase inhibitory action potentiates the effects of adenosine on platelets.


2021 ◽  
pp. 155633162199200
Author(s):  
Ravi Gupta ◽  
Anil Kapoor ◽  
Sourabh Khatri ◽  
Dinesh Sandal ◽  
Gladson David Masih

Background: Osteoarthritis (OA) in the anterior cruciate ligament (ACL)–deficient knee is seen in approximately 50% of affected patients. Possible causes include biochemical or biomechanical changes. Purpose: We sought to study the correlation between inflammatory cytokines and chondral damage in ACL-deficient knees. Methods: Seventy-six male patients who underwent ACL reconstruction were enrolled in a cross-sectional study. Synovial fluid was aspirated before surgery and analyzed for levels of the inflammatory cytokines tumor necrosis factor-α, interleukin-1 (IL-1), and interleukin-6 (IL-6). At the time of ACL reconstruction, the severity of chondral damage was documented as described by the Outerbridge classification. Results: Patients with grade 2 or higher chondral damage were observed to have elevated IL-6 levels when compared to patients who had no chondral damage. Interleukin-6 levels had no correlation with the duration of injury. Conclusion: Elevated levels of IL-6 in synovial fluid were associated with chondral damage in ACL-deficient knees. Further study is warranted to determine whether inflammatory cytokines contribute to the development of OA of the knee after ACL injury.


Author(s):  
Giulio Cavalli ◽  
Alessandro Larcher ◽  
Alessandro Tomelleri ◽  
Lorenzo Dagna
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