Cytokine antagonist

Goldie, A.S., Fearon, K.C.H., Ross, J.A., Barclay, R., Jackson, R.E., Grant, I.S., Ramsay, G., Blyth, A.S., Howie, J.C. Natural cytokine antagonists and endogenous antiendotoxin core antibodies in sepsis syndrome, JAMA 274 (1995) 172-177. 

The use of cytokine antagonists (monoclonal antibodies to cytokines) used in the management of rheumatoid arthritis and Crohn s disease has some beneficial effect on Graves orbitopathy. A recent stndy of 10 patients with mild to moderately severe Graves orbitopathy showed that the administration of etanercept, an antitrunor necrosis fector drug (25 mg a week for 3 months) was associated with a significant improvement of the clinical activity score and ophthalmopathy index in approximately 60% of patients. 

Anti-IL-4 antibodies could be interesting as a means of correcting the balance between Thl and Th2 cells in Th2 polarized situations. However, it has been reported that the peripheral blood of allergic individuals contains long-lived allergen-specific B cells that have already switched to IgE production and that are not sensitive to IL-4 and IL-13 treatment. These results may have implications on attempts to use cytokines or cytokine antagonists in therapy of a type I allergy. ... 

Catania A. Airaghi L, Motta P, Manfredi MG, Annoni G, Pettenati C, et al. Cytokine antagonists in aged subjects and their relation with cellular immunity. J Gerontol Biol Sci 1997 52A B93-B97. 

Debets R, Savelkoul H F (1994). Cytokine antagonists and their potential therapeutic use. Immunol. Today. 15 455-458. 

The administration of recombinant cytokines or cytokine receptors in experimental animal models of infection has proven to be a powerful tool to study the biological effects of specific cytokine mediators. However, cytokine- based immunotherapy is often complicated by significant toxicity, especially when cytokines or cytokine antagonists are given systemically. This is particularly true... 

In the absence of selective antagonists, cytokines have been classified either on the basis of common functional properties or on the stmctural characteristics of their receptors. 

Since the recognition of at least two av integrin pathways for cytokine-mediated angiogenesis, av 33 and av 35 antagonists may be more effective in certain indications as compared to a specific anti- av 33. However, further work is needed to document this notion. 

In addition to inhibiting cytokine synthesis by glucocorticoids, cytokine effects can be prevented by scavenging the cytokine either with neutralizing antibodies or soluble receptors or by blocking the respective cytokine plasma membrane receptors with blocking antibodies or receptor antagonists. 

IFN- 3 reduces the induction by inflammatory cytokines of adhesion molecules and of MHC class I and II complex on endothelial cells, a process preceding attachment and transendothelial migration of T-cells. These anti-inflammatory effects of IFN- 3 exemplify antagonistic actions of type I and type IIIFN. There is, indeed, much clinical evidence for the involvement of IFN-y in inflammatory processes - through activation of iNOS and subsequent secretion of NO - leading to the establishment of autoimmune diseases as for instance in rheumatoid arthritis. 

Attaching some short peptidic sequences to adamantane makes it possible to design novel antagonists. The bradykinin antagonist, which is used as an anticancer agent, is an example. The adamantane-based peptidic bradykinin analog was utilized in strucmre-activity relationship (SAR) studies on the bradykinin receptors and showed a potent activity in inhibition of bradykinin-induced cytokine release and stimulation of histamine release [142]. 

The purported prophylactic use of Japanese herbal medicines to combat neuronal ageing has been related to their free-radical scavenging activity (Hiramatsu a al., 1992). Inhibition of the pro-inflammatory effects of cytokine interleukin-1 by recombinant endogenous interleukin-1 receptor antagonist in experimental rats is associated with alleviation of excitotoxic neuronal damage, an action which has also been related to the antiinflammatory effect of lipocortin 1 (Relton and Roth well, 1992). 

Azelastine Hrreceptor antagonist, mast cell stabilizer May inhibit cytokine release... 

Pro- and Anti-Inelammatory Cytokines and Circulating Natural Antagonists... 

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