Antiinflammatory therapy effects additive, alter decline of pulmonary function

[Guest guest]

Immunotherapy Weekly

                                 March 5, 2003

HEADLINE: CYSTIC FIBROSIS: Antiinflammatory therapy effects additive, alter

decline of pulmonary function

   According to a study in the United States, " Some of the most important

pathobiology in cystic fibrosis occurs not as a direct result of impaired

chloride transport, but the downstream consequences of defective CFTR

function,

particularly the lung infection and inflammation that ultimately takes the

lives

of most patients.

    " Interrupting the vicious cycle of infection and inflammation is effective

in

slowing the course of the disease, and antibiotics have long been the staple

of

pulmonary therapy. However, limiting the inflammatory response in the CF lung

is

also effective.

    " High dose ibuprofen clearly retards progression of lung disease, but also

entrains adverse events that mar its therapeutic utility, so alternative

antiinflammatory agents are necessary. Because of the remarkable therapeutic

success of ibuprofen, consideration should be given to finding less toxic

alternatives.

    " However, it is also appropriate to consider the mechanisms by which the

inflammatory response occurs in the CF lung, and identify sites to interrupt

it.

Sites at which therapeutic intervention is possible are the neutralization of

cytokines such as tumor necrosis factor-alpha, interleukin (IL-1beta), or

IL-8

with specific antibodies or receptor antagonists, inhibition of the

intracellular signaling cascades that result in cytokine production (for

example, at the level of p38 MAP kinase), application of cytokines such as

IL-10

that are themselves anti-inflammatory, or modulating the arachidonic acid

cascade with inhibitors directed at leukotriene B-4.

    " In addition, interventions designed to limit the consequences of the

inflammatory response, such as protease inhibitors and reagents to limit the

ill

effects of DNA accumulation in airways, are in use. To limit adverse effect

and

concentrate the therapeutic effect, there may be value in targeting delivery

of

the therapeutic reagents to the inflamed site, either by specifically

directing

systemic delivery or by exploitation of the aerosol route, " stated M.W.

Konstan

and coauthors, Case Western Reserve University, School of Medicine.

   Konstan and coauthors concluded: " Treating the inflammatory response is

important, for the data from the ibuprofen study show that the effects of

antiinflammatory therapy are additive or even synergistic with intensive

conventional therapy and alter the rate of decline of pulmonary function, and

therefore benefits for survival of patients with CF are to be expected. "

   Konstan and colleagues published the results of their study in Advanced

Drug

Delivery Reviews (Pharmacological approaches for the discovery and

development

of new anti-inflammatory agents for the treatment of cystic fibrosis. Adv

Drug

Delivery Rev, 2002;54(11):1409-1423).

   The corresponding author for this report is M.W. Konstan, Case Western

Reserve University, School of Medicine, Department Pediatrics, 11100 Euclid

Avenue, Cleveland, OH 44106, USA.

   To subscribe to the journal Advanced Drug Delivery Reviews, contact the

publisher: Elsevier Science BV, PO Box 211, 1000 AE Amsterdam, Netherlands.

   The information in this article comes under the major subject areas of

Pharmacology, Immunology and Pulmonary Medicine.

   This article was prepared by Immunotherapy Weekly editors from staff and

other reports.

    http://www.NewsRx.net

Becki

YOUR FAVORITE LilGooberGirl

YOUNGLUNG EMAIL SUPPORT LIST

www.topica.com/lists/younglung

Pediatric Interstitial Lung Disease Society

http://groups.yahoo.com/group/InterstitialLung_Kids/