Anti-inflammatory Action Of Corticosteroids Research Articles

Effects of genetic factors to inhaled corticosteroid response in children with asthma: a literature review.

Numerous studies have examined the association between pharmacogenetic effects and the response to inhaled corticosteroids (ICS) in patients with asthma. In fact, several single nucleotide polymorphisms of a number of candidate genes have been identified that might influence the clinical response to ICS in children with asthma. Their direct or indirect effects depend on their role in the inflammatory process in asthma or the anti-inflammatory action of corticosteroids, respectively. Among the genes identified, variants in T-box 21 (TBX21) and Fc fragment of IgE receptor II (FCER2) contribute indirectly to the variability in the response to ICS by altering the inflammatory mechanisms in asthma, while other genes such as corticotropin releasing hormone receptor 1 (CRHR1), nuclear receptor subfamily 3 group C member 1 (NR3C1), stress induced phosphoprotein 1 (STIP1), dual specificity phosphatase 1 (DUSP1), glucocorticoid induced 1 (GLCCI1), histone deacetylase 1 (HDAC), ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3), and vascular endothelial growth factors (VEGF) directly affect this variability through the anti-inflammatory mechanisms of ICS. The results to date indicate various potential genetic factors associated with the response to ICS, which could be utilized to predict the individual therapeutic response of children with asthma to ICS. Clinical trials are underway and their results are greatly anticipated. Further pharmacogenetic studies are needed to fully understand the effects of genetic variation on the response to ICS in children with asthma.

Relationship of functional status of persons having chronic ‘non-affective psychosis’ with anxiety, depression and self-esteem of family caregivers

Acute pain associated with herpes zoster (HZ) is the most debilitating symptom, which if not treated in early phase may lead to postherpetic neuralgia (PHN), a potentially crippling disorder with prolonged intractable chronic pain. The socioeconomic consequences secondary to prolonged severe pain include decreased socialization, depression, fatigue, restricted daily activities, and poor quality of life. HZ and PHN impose a significant economic burden in the form of direct inpatient care and loss of productivity. Early interventional treatments attenuate central sensitization by interrupting the transmission of nociceptive afferent impulses to the central nervous system and minimize nerve damage by improving blood flow to the nervous tissue in addition to the local anti-inflammatory action of corticosteroids. Interventions treatment options have been increasingly used as a part of multimodal approach in the management of acute pain of HZ in addition to pharmacological agent. This article reviews the various interventional treatment options which have used in the recent years for the management of acute pain of HZ and subsequent prevention of PHN.

Corticosteroid Resistance in Airway Disease

Resistance to the antiinflammatory effects of corticosteroids is very uncommon in asthma but common in chronic obstructive pulmonary disease. Recent understanding of the molecular mechanisms involved in the antiinflammatory actions of corticosteroids has revealed that there are several possible mechanisms for corticosteroid resistance. Certain cytokines activate p38 mitogen-activated protein kinase, which may interfere with the nuclear localization of glucocorticoid receptors (GRs). In other patients, nuclear localization of GR is normal but there is a reduction in acetylation of a lysine residue in histone-4, thus leading to impaired activation of certain antiinflammatory genes. In chronic obstructive pulmonary disease and severe asthma, oxidative stress may reduce the activity and expression of certain histone deacetylases and therefore interfere with the antiinflammatory action of corticosteroids. These mechanisms suggest that there may be several therapeutic approaches to treating corticosteroid resistance in the future, including antioxidants, p38 mitogen-activated protein kinase inhibitors, and theophylline, which activates histone deacetylases.

A review of the preclinical and clinical data of newer intranasal steroids used in the treatment of allergic rhinitis

The anti-inflammatory activity of corticosteroids has prompted the exploration of their use in the treatment of allergic rhinitis. The development of intranasal steroids has resulted in several agents with quick actions, localized effects, and great efficacy in the treatment of seasonal allergic rhinitis and the prophylactic management of perennial rhinitis. This article presents a concise review of the preclinical and clinical evidence with these new agents and provides data-based guidance for the selection of optimal agents. The survey reveals that mometasone furoate, a new inhaled steroid with topical activity, has the greatest binding affinity for the glucocorticoid receptor, followed by fluticasone propionate, budesonide, triamcinolone acetonide, and dexamethasone. Mometasone furoate also has strong anti-inflammatory activity, with IL-4 and IL-5 inhibition activities equivalent to those of fluticasone propionate. Clinically, both mometasone furoate and fluticasone propionate appear to be well tolerated, to have quick onsets of action, and to be equivalent in efficacy in the treatment of seasonal allergic and perennial rhinitis. Of the intranasal steroids currently available, mometasone furoate has been shown to have the least systemic availability and, consequently, is expected to have the fewest systemic side effects. Some suppression of overnight cortisol levels has been reported with fluticasone propionate (indicative of hypothalamic-pituitary-adrenal axis suppression). (J Allergy Clin Immunol 1999;104:150-8.)

Mechanisms of intranasal steroids in the management of upper respiratory allergic diseases

Intranasal steroids have proved to be the most effective class of drugs in reducing the symptoms of allergic rhinitis. This clinical response reflects the broad anti-inflammatory activity that has been demonstrated for corticosteroids. Single doses of topical corticosteroids administered before nasal allergen challenge block the late-phase reaction, whereas repeated dosing with intranasal steroids blocks both the early and the late response, as well as the priming phenomenon. Nasal inflammation is accomplished through a number of effector cells and mechanisms, which in turn are produced by director cells through the release of cytokines and chemokines. The anti-inflammatory action of corticosteroids is largely effected through blocking the synthesis and release of these cytokines/chemokines. (J Allergy Clin Immunol 1999;104:S138-43)

??-agonists increase inflammatory mediator generation and block anti-inflammatory actions of corticosteroids

??-agonists increase inflammatory mediator generation and block anti-inflammatory actions of corticosteroids

Autoantibodies to annexins: a diagnostic marker for cutaneous disorders?

Annexins/lipocortins are a group of structurally related calcium and lipid binding proteins which have been implicated as mediators of the anti-inflammatory action of corticosteroids. Autoantibodies against annexin-1 have been reported in association with autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis and their presence has been hypothesized as the reason for the steroid resistance phenomenon. In this study we investigated IgG- and IgM-autoantibodies against annexin-1,-2,-3,-4,-5 and -6 in sera of 221 patients with skin disorders and 114 healthy blood donors with newly established ELISAs. Patients were clustered into 5 groups according to their diagnosis: autoimmune diseases, psoriasis, leg ulcer, malignant melanoma, and miscellaneous diseases. Autoantibodies directed against each annexin were detectable in all investigated groups, in the control group as well as in the disease groups, without displaying any significant correlation to any of the disease states. The homogenous distribution of annexin-autoantibodies throughout the control group and all the disease groups studied, do not support the implication of annexin-autoantibodies in pathophysiological states and make them an unlikely candidate for use as a diagnostic marker.

Lipocortins, mediators of the anti-inflammatory actions of corticosteroids?

La cortisone inhibe l'inflammation en inhibant la phospholipase A par l'intermediaire de facteurs proteiques: les lipocortines, appartenant a la famille des proteines fixant le Ca 2+ . Ce document fait le point sur les caracteristiques et le role de ces molecules

Possible participation of insulin in the control of vascular permeability

Swelling induced in the rat's paw by chemical irritants has previously been shown to be markedly reduced in diabetic rats. Since diabetic animals rendered normoglycemic still presented inhibited responses whereas insulin administration reversed the inhibition, insulin might be expected to influence the development of the oedema. This might be done either directly or through an exacerbated action of adrenal corticosteroids secondary to insulin deficiency. Swelling reactions (dextran, carrageenin), as well as vascular permeability evoked by electrical stimulation of sensory nerves are now shown to be reduced in diabetic-adrenalectomized animals, as much as in diabetic rats, thus suggesting that the inhibition is not likely to depend on an anti-inflammatory action of corticosteroids. Electron microscopic investigation revealed that subdermal vessels of normal rats following i.d. injections of histamine were congested and endothelial openings easily found. In contrast, the endothelial junctions were usually closed in diabetic rats. These functional alterations might be related to insulin deficiency. It is concluded that the integrity of microcirculatory responses to noxious stimuli might, at least partially, depend on the availability of insulin.

Alteration of proline hydroxylase activity by glucocorticoids

The biochemical mechanism by which glucocorticoids affect collagen metabolism was investigated. Triamcinolone, hydrocortisone and methylprednisolone significantly decreased liver proline hydroxylase activity in vivo to an extent unrelated to the decrease of protein in the 15,000 g supernatant. Triamcinolone inhibited liver proline hydroxylase in a dose-dependent manner in vivo. An observed elevation of liver proline hydroxylase activity in adrenalectomized animals was decreased to control levels by hydrocortisone treatment. Subdermal implants of polyvinyl sponges were used to induce granuloma growth as a model system of inflammation. The anti-inflammatory activity of corticosteroids was correlated with inhibition of proline hydroxylase activity in granuloma tissue. The data indicate that corticosteroids decrease collagen synthesis by inhibiting the proposed rate-limiting enzyme. This inhibitory effect on collagen metabolism is correlated with observed anti-inflammatory activity.

Kinins and anti-inflammatory steroids.

1. This investigation was designed to re-examine the possibility that anti-inflammatory steroids interfere with the kinin-forming system.2. We conclude that the anti-inflammatory action of corticosteroids cannot be explained by the inhibition of kinin formation. This view is based on the following findings.3. Neither hydrocortisone nor prednisolone nor dexamethasone inhibited the activation or activity of intrinsic plasma kinin forming enzymes resulting from dilution, incubation with kininase inhibitors, or exposure to glass, monosodium urate microcrystals or to precipitated complexes of rheumatoid factor and aggregated human gamma-globulin.4. Hydrocortisone did not inhibit the action of the active kinin-forming enzymes, human salivary or urinary kallikrein, or plasmin on purified kininogen.5. Hydrocortisone, prednisolone and dexamethasone did not inhibit the hydrolysis of benzoyl-arginine-ethyl ester by human plasmin, plasma kallikrein or hog pancreatic kallikrein.6. Kinin formation occurred normally in plasma taken from two patients receiving betamethasone and one receiving prednisone.

Responses of skin blood vessels to bradykinin, histamine and 5‐hydroxytryptamine

1. The responses of human cutaneous blood vessels to intradermal injection of bradykinin, histamine and 5-hydroxytryptamine (serotonin) are studied in order to evaluate the ability of these agents to mediate the vascular changes of sustained acute inflammation in the skin.2. Bradykinin produces erythema, owing to a direct effect on blood vessels, and wealing. Dose-response studies indicate that bradykinin is more potent than serotonin or histamine in respect of wealing.3. The response to serotonin differs qualitatively as well as quantitatively according to dose. High doses cause wealing and erythema with the characteristics of an axon reflex flare, but low doses produce erythema by a local effect without wealing.4. Using the technique of arterial occlusion, the occurrence of tachyphylaxis in respect of wealing was demonstrated with histamine and serotonin, but not with bradykinin. This evidence suggests that of the three agents, only bradykinin can mediate increased vascular permeability in sustained acute inflammation.5. The specificity of tachyphylaxis and the failure of anti-histamine to antagonize bradykinin wealing suggest that bradykinin and histamine act on separate blood vessel receptors.6. Corticosteroids do not inhibit wealing due to a wide range of doses of bradykinin. The anti-inflammatory activity of corticosteroids may therefore be due to reduced formation of kinins.