Antiinflammatory Steroids

Popper, T. L.; Watnick, Arthur S.

doi:10.1016/b978-0-12-623901-0.50017-1

Cited by 17 publications

(7 citation statements)

References 101 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, the increase in BAL EOs 24 h after OVA challenge was reduced by treatment with beta methasone, prednisolone and hydrocortisone. The rank or der potency o f these corticosteroids is similar to that report ed for their anti-inflammatory activity in humans [33]. Be tamethasone, which was the most potent of the three corticosteroids used, also prevented the reduction o f EOs in bone marrow 24 h after OVA challenge.…”

Section: Discussionsupporting

confidence: 52%

Characterization of a Murine Model of Allergic Pulmonary Inflammation

Kung¹,

Jones²,

Adams³

et al. 1994

Int Arch Allergy Immunol

210

165

View full text Add to dashboard Cite

Pulmonary inflammation with eosinophil (EOs) infiltration is a prominent feature of allergic respiratory diseases such as asthma. In order to study the cellular response during the disease development, an animal model of IgE-mediated pulmonary inflammation with characteristic eosinophilia is needed. We developed a method for inducing severe pulmonary eosinophilia in the mouse and also studied the numbers of EOs in blood and bone marrow and the response to corticosteroid treatment. Animals were sensitized with alum-precipitated ovalbumin (OVA) and challenged with aerosolized OVA 12 days later when serum IgE levels were significantly elevated. Four to eight hours after challenge there were moderate increases in the number of EOs in the bone marrow and peripheral blood, but only a few EOs were observed in the lung tissue and in bronchoalveolar lavage (BAL) fluid. Twenty-four hours after challenge, there was a marked reduction of EOs in bone marrow, while the number of EOs peaked in the perivascular and peribronchial regions of the lung. Forty-eight hours after challenge, the highest number of EOs was found in the BAL fluid, making up > 80% of all cells in that compartment. The high levels of EOs in the lung tissue and BAL fluid lasted for 2-3 days and was followed by a more moderate but persistent eosinophilia for another 10 days. Nonsensitized animals showed no significant changes in the number of EOs in BAL fluid, lungs, blood or bone marrow. Histopathological evaluation also revealed epithelial damage, excessive mucus in the lumen and edema in the submucosa of the airways. The pulmonary eosinophilia and decrease in bone marrow EOs induced by OVA challenge responded well to treatment with several standard corticosteroids. The rank order of steroid potency for inhibition of pulmonary eosinophilia was betamethasone > prednisolone > hydrocortisone. Because mice are extremely useful for immunological studies, this model can be invaluable to study the effects of cytokines on pulmonary inflammation.

show abstract

Section: Discussionsupporting

confidence: 52%

Characterization of a Murine Model of Allergic Pulmonary Inflammation

Kung¹,

Jones²,

Adams³

et al. 1994

Int Arch Allergy Immunol

210

165

View full text Add to dashboard Cite

show abstract

“…The potencies of steroidal antedrugs showed little dependencies on the 17 α -OH functional group. The improved potency of the fluorinated GCs is in consistence with previous finding that fluorination particularly at 9 α -position enhances all the biological activities of glucocorticoids 111–113. Esterification of 21-OH67 of 9α-fluoro prednisolone derivatives ( 38 where X = F and 21-OH is replaced with different alkyl esters) demonstrated that 9 α -fluoro, 16 α -methoxy carbonyl, and 21-pivalyl group increased the topical anti-inflammatory potencies by 2-folds with the exception of other esters.…”

Section: Pharmacology Of Anti-inflammatory Steroidal Antedrugssupporting

confidence: 88%

Synthesis and Pharmacology of Anti-Inflammatory Steroidal Antedrugs

Khan

Lee

2008

Chem. Rev.

View full text Add to dashboard Cite

“…Philip Hench offered (pre)cautionary advice 60 years ago. Twenty-odd years later this was reiterated by Popper and Watnick (1974). In surveying antiinflammatory steroids, they wrote:…”

Section: A Summing-upmentioning

confidence: 94%

“…Such effects as suppression of adrenal function, osteoporosis and thinning of the skin have not been diminished by increasing the anti-inflammatory potency of the corticosteroid. (Popper and Watnick 1974) • The past 40 years have seen instead the development of more potent (and toxic) NSAIDs to reduce dependence on steroids. Tragically this thrust culminated in the disaster of the highly selective Cox-2 inhibitors.…”

Section: A Summing-upmentioning

confidence: 98%

Anti-inflammatory glucocorticoid drugs: reflections after 60 years

Whitehouse

2010

Inflammopharmacol

View full text Add to dashboard Cite

This review considers the problem of the serious concomitant side effects of powerful anti-inflammatory drugs modelled upon the principal human glucocorticoid hormone, cortisol. The very nature of the original bio-assays to validate their cortisol-like hormonal and anti-inflammatory activities ensured that pleiotropic toxins were selected for clinical studies. Other complicating factors have been (1) considerable reliance on bio-assays conducted in laboratory animals that primarily secrete corticosterone, not cortisol, as their principal anti-inflammatory adrenal hormone; (2) some differences in the binding of xenobiotic cortisol analogues (vis á vis cortisol) to transport proteins, detoxifying enzymes and even some intra-cellular receptors; (3) the "rogue" properties of these hormonal xenobiotics, acting independently of--but still able to suppress--hormonal mechanisms regulating endogenous cortisol; and (4) problems of intrinsic/acquired "steroid resistance", diminishing their clinical efficacy, but not necessarily all their toxicities. The rather gloomy conclusion is that devising new drugs to reproduce the effect of multi-potent hormones may be a recipe for disaster, in contexts other than simply remedying an endocrine deficiency. Promising new developments include "designed" combination therapies that allow some reduction in total steroid doses (and hopefully their side effects); sharpening strategies to limit the actual duration of steroid administration; and resurgent interest in searching for more selective analogues (both steroidal and non-steroid) with less harmful side effects. Some oversights and neglected areas of research are also considered. Overall, it now seems timely to engage in some drastic rethinking about (retaining?) these "licensed toxins" as fundamental therapies for chronic inflammation.

show abstract

Antiinflammatory Steroids

Cited by 17 publications

References 101 publications

Characterization of a Murine Model of Allergic Pulmonary Inflammation

Characterization of a Murine Model of Allergic Pulmonary Inflammation

Synthesis and Pharmacology of Anti-Inflammatory Steroidal Antedrugs

Anti-inflammatory glucocorticoid drugs: reflections after 60 years

Contact Info

Product

Resources

About