Pimecrolimus Reduces Eosinophil Activation Associated with Calcium Mobilization

Plager, Douglas A.; Henke, Susan A.; Matsuwaki, Yoshinori; Madaan, Arvind; Squillace, Diane L.; Dierkhising, Ross A.; Kita, Hirohito

doi:10.1159/000189194

Cited by 14 publications

(12 citation statements)

References 55 publications

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“…Eosinophil degranulation has been implicated in the pathology of bronchial asthma and is closely associated with disease activity [15,16,17]. Superoxide generation is another important proinflammatory function of eosinophils [18] and might induce oxidative tissue damage [19,20]. Actually, oxidative stress has been shown to increase in patients with asthma [21].…”

Section: Discussionmentioning

confidence: 99%

Differential Activation of Eosinophils by Bacteria Associated with Asthma

Hosoki

Nakamura

Kainuma

et al. 2013

Int Arch Allergy Immunol

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Background: It has been suggested that there is a complex interaction between microbiota and various human diseases. Some bacteria have been reported to be involved in the inception and progression of asthma, and others in the protection against asthma. We know very little about the mechanisms by which bacteria do harm or good with regard to asthma. This study investigated whether bacteria exert differential effects on the functions of eosinophils, major effector cells in airway inflammation in asthma. Methods: Eosinophils were purified from healthy adult volunteers by Percoll density gradient centrifugation and negative immunomagnetic bead selection using anti-CD16 microbeads. Three kinds of heat-killed bacteria that have been implicated in asthma, namely Staphylococcus aureus (SA), Haemophilus influenzae (HI) and a Prevotella sp. (PS), were tested for their effects on the secretion of eosinophil-derived neurotoxin (EDN), the generation of superoxides and the production of cytokines/chemokines. Results: SA, but not HI or PS, induced significant EDN release in a dose-dependent manner. Superoxide generation was significantly enhanced by each of the bacterial species, but most strongly by SA, which induced significantly greater TNF-α production by eosinophils than either HI or PS. Conversely, interleukin 10, an anti-inflammatory cytokine, was more strongly induced by HI and PS than by SA. Conclusions: Bacteria exert differential effects on eosinophils. Based on these results, SA may be involved in the exacerbation of, and HI and PS in the inhibition of, eosinophilic inflammation in asthma.

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Section: Discussionmentioning

confidence: 99%

Differential Activation of Eosinophils by Bacteria Associated with Asthma

Hosoki

Nakamura

Kainuma

et al. 2013

Int Arch Allergy Immunol

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“…Immobilized IgG, IgA, and secretory IgA (sIgA) induce eosinophil degranulation [13,23], and various lipid mediators (such as PAF) and cytokines (such as IL-5) also activate eosinophils [21]. Furthermore, activated eosinophils release granule proteins (for example major basic protein and EDN), lipid mediators, reactive oxygen intermediates, cytokines and enzymes [2].…”

Section: Discussionmentioning

confidence: 99%

“…Immediately after eosinophils were placed, the absorbance at 550 nm was analyzed in a Thermomax plate reader (Molecular Devices, Sunnyvale, Calif., USA) followed by readings every 15–30 min. Conversion of absorbance to nanomoles of cytochrome c reduced per 1 × 10 6 eosinophils used the following equation: 19.1 × (absorbance – absorbance time 0 )/0.05 = nmol cytochrome c reduced/10 6 cells [20,21]. …”

Section: Methodsmentioning

confidence: 99%

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Antigen-Specific IgG and IgA, but Not IgE, Activate the Effector Functions of Eosinophils in the Presence of Antigen

Muraki

Gleich

Kita

2010

Int Arch Allergy Immunol

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Background: Activated eosinophils are thought to play an important role in allergic inflammation. Prior reports suggest that eosinophils have receptors recognizing IgA, IgG and IgE; however, little is known regarding the direct effects of antigens and antigen-specific immunoglobulins on the functions of eosinophils. Methods: To investigate eosinophil activation by antigens mediated by the various antigen-specific immunoglobulins, we used dansyl-conjugated bovine serum albumin (DNS-BSA) and recombinant dansyl-specific antibodies (human IgG 1–4, IgA and IgE). Eosinophils from healthy donors were incubated in the wells coated with dansyl-specific immunoglobulins with or without DNS-BSA. Eosinophil activation was monitored by superoxide production and eosinophil-derived neurotoxin (EDN) release. Results: Superoxide production and EDN release by eosinophils were induced by the dansyl-specific reaction via all IgG subclasses (IgG 1–4) and IgA in the presence of DNS-BSA; the responses were not observed in the absence of antigen, DNS-BSA. The immune complexes (ICs) of DNS-BSA and dansyl-specific IgE did not induce these responses. Furthermore, IgE ICs did not enhance eosinophil activation stimulated with various immunoglobulins, IL-5 or platelet-activating factor. Conclusion: These data suggest that ICs of antigens and antigen-specific IgGs and IgA, but not IgE, in inflamed tissues may activate eosinophils and play an important role in allergic inflammation.

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“…[27] At nanomolar concentrations, pimecrolimus inhibits the production and release of inflammatory cytokines (interferon-g, IL-2, IL-4, IL-5, IL-10, and tumor necrosis factor-a); [23][24][25]28,29] the drug also inhibits the release of inflammatory cytokines and mediators (e.g. [28] Pimecrolimus also inhibits superoxide anion production and eosinophil-derived neurotoxin release by »30-50% [31] and increases keratinocyte expression of antimicrobial peptides and the capacity to inhibit Staphylococcus aureus growth. [30] Other effects of pimecrolimus on human skin include reductions in the expression of cleaved caspase-3 in the epidermis and Fas receptor expression on keratinocytes, [29] and reduced lymphocyte and eosinophil counts.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Topical Pimecrolimus

Yang¹,

Curran²

2009

Pediatric Drugs

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Topical pimecrolimus 1% cream (Elidel) [hereafter referred to as topical pimecrolimus] is a nonsteroidal alternative in the treatment of pediatric atopic dermatitis. In vehicle-controlled, short-term, continuous-use trials in pediatric patients with mild to moderate atopic dermatitis, topical pimecrolimus was effective in treating disease symptoms. Topical pimecrolimus was effective in preventing disease flares and reducing the need for topical corticosteroids in longer term, intermittent-use trials. In addition, topical pimecrolimus was associated with improvements in the health-related quality of life (HR-QOL) of pediatric patients with atopic dermatitis and their parents. In vehicle-controlled trials, topical pimecrolimus was generally as well tolerated as vehicle. Topical pimecrolimus showed similar efficacy to topical tacrolimus 0.03% ointment (hereafter topical tacrolimus) in a short-term, continuous-use trial and the two agents had a generally similar tolerability profile. Although comparative data between topical pimecrolimus and topical corticosteroids are lacking in pediatric patients, and the long-term tolerability (beyond 1-2 years) of topical pimecrolimus is yet to be established, topical pimecrolimus is a useful agent in the management of pediatric patients with mild to moderate atopic dermatitis who do not achieve satisfactory treatment with other topical pharmacologic treatments, including topical corticosteroids.

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Pimecrolimus Reduces Eosinophil Activation Associated with Calcium Mobilization

Cited by 14 publications

References 55 publications

Differential Activation of Eosinophils by Bacteria Associated with Asthma

Differential Activation of Eosinophils by Bacteria Associated with Asthma

Antigen-Specific IgG and IgA, but Not IgE, Activate the Effector Functions of Eosinophils in the Presence of Antigen

Topical Pimecrolimus

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