Page 1210 - Clinical Immunology_ Principles and Practice ( PDFDrive )

1174 ParT TEN Prevention and Therapy of Immunological Diseases

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In contrast, NCX-1015 did not activate primary osteoclast activity morning stiffness. Further clinical developments seem likely
in vitro, whereas prednisolone did. This lack of adverse effect of to follow (e.g., new GCR ligands and liposome encapsulation),
NCX-1015 seems to be chiefly caused by NO. It has been suggested all with a view to improving the risk–benefit ratio of GC therapy
that posttranslational modification of GCR (tyrosine nitration) and the well-being of patients.
by NCX-1015 may explain its enhanced antiinflammatory activity.
Moreover, NCX-1015 potently stimulates IL-10 production, sug- ON THE HOrIZON
gesting that nitrosteroids induce Tregs that negatively modulate
inflammation. However, further work is needed to confirm the • Selective activators of transrepression (SEGRA)
• Nitrosteroids (with effect of nitric oxide on endothelium)
utility of nitrosteroids in clinical practice. • Modified release steroids
Long-Circulating Liposomal Glucocorticoids • Liposomal encapsulation
• Optimized combinations with biologicals
The antiinflammatory efficacy of GCs can be improved by the
additional benefits of nongenomic actions at high GC concentra- ACKNOWLEDGMENTS
tions. This has led to the use of long-circulating liposomal GCs
in experimental models. In rats with experimental autoimmune This chapter has been revised and updated from the version in
encephalitis, GC-containing liposomes accumulated at sites of the previous edition. The editors are grateful to Frank Buttgereit,
inflammation, reaching concentrations >10–5 mol/L for ≥18 Hans Bilsma and Markus Seibel for their contributions to previous
hours. These liposomes may be therapeutically superior to editions and for their permission to let us update the chapter.
conventional intravenous high-dose GC therapy, as evidenced
by their successful use in rats with adjuvant-induced arthritis. A Please check your eBook at https://expertconsult.inkling.com/
single injection of 10 mg/kg liposomal prednisolone phosphate for self-assessment questions. See inside cover for registration
resulted in complete remission of the inflammatory response details.
for almost a week. In contrast, the same dose of unencapsulated
prednisolone phosphate did not reduce inflammation and had
only a slight effect after repeated daily injections. It may be that REFERENCES
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