Antiinflammatory Therapies for Cystic Fibrosis: Past, Present, and Future

Abstract

Inflammation is a major component of the vicious cycle characterizing cystic fibrosis pulmonary disease. If untreated, this inflammatory process irreversibly damages the airways, leading to bronchiectasis and ultimately respiratory failure. Antiinflammatory drugs for cystic fibrosis lung disease appear to have beneficial effects on disease parameters. These agents include oral corticosteroids and ibuprofen, as well as azithromycin, which, in addition to its antimicrobial effects, also possesses antiinflammatory properties. Inhaled corticosteroids, colchicine, methotrexate, montelukast, pentoxifylline, nutritional supplements, and protease replacement have not had a significant impact on the disease. Therapy with oral corticosteroids, ibuprofen, and fish oil is limited by adverse effects. Azithromycin appears to be safe and effective, and is thus the most promising antiinflammatory therapy available for patients with cystic fibrosis. Pharmacologic therapy with antiinflammatory agents should be started early in the disease course, before extensive irreversible lung damage has occurred.

Bioactive cyclobutane-containing alkaloids

“…Plants such as autumn crocus or meadow saffron (C. autumnale) and glory lily (Gloriosa superba) contain colchicine alkaloids. Colchicine is a mitotic inhibitor that terminates cell division and is thought to have an antiinflammatory effect as an inhibitor of leukocyte migration and the secretion of inflammatory glycoproteins [144,145]. The present medicinal uses for colchicine and its derivatives are mainly in the treatment of gout; as well, it is being investigated for its potential use as an anticancer drug [146,147].…”

“…The oxysceptrins are characterized by their aminoimidazolinone group, the ageliferins, by a unique cyclohexene-based skeleton [220]. Debromosceptrin (144) and two known pyrrole analogs (145) and (146) were also found in extract of the Caribbean sponge A. conifera collected from Belize [221]. Oxysceptrin (148) from the Okinawan marine sponge Agelas cf.…”

Novosti v Obravnavi Pljučne Bolezni Pri Otrocih in Mladostnikih S Cistično Fibrozo

“…Povišane koncentracije provnetnih citokinov se nahajajo v izmečku, serumu in bronhoalveolnem izpirku (BAL). 29 Azitromicin zmanjšuje vnetje v dihalnih poteh, zavira pa tudi komunikacijo med bakterijami (t. i. quorum sensing). Raziskave so dokazale, da redna uporaba azitromicina zmanjša število poslabšanj in izboljša pljučno funkcijo.…”

Cystic Fibrosis Therapeutics

“…For example, although azithromycin is commonly considered to be an antibiotic, this macrolide also demonstrates substantial impacts on infl ammation both in vitro 25 and in clinical trials 26 ; more than one review article has even referred to azithromycin as among the most promising antiinfl ammatory therapies for CF. 27,28 Similarly, a recent Two additional antibiotic preparations given by the inhaled route, each using an aminoglycoside, are also in development. Arikace is a liposomally encased preparation of amikacin, providing sustained release and rapid delivery times.…”