Anti-Inflammatory Effect of FK-506 on Human Skin Mast Cells

Paulis, Amato de; Stellato, Cristiana; Cirillo, R; Ciccarelli, Andrea; Oriente, Alfonso; Marone, Gianni

doi:10.1111/1523-1747.ep12614216

Cited by 169 publications

(131 citation statements)

References 31 publications

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“…We also acknowledge that the number of subjects in our study was limited, but it exceeded the numbers in the other studies they cite. 4,5 We therefore do not understand why their conclusions, based on data from fewer subjects, are "correct" and ours, based on data from more subjects, are "incorrect." Although there is little doubt that biochemical abnormalities in receptor function follow the prolonged use of b 2 -adrenergic agonists, the work that Drs.…”

Section: Exercise-induced Asthmamentioning

confidence: 75%

“…3 Pharmacologic concentrations of tacrolimus exert antiinflammatory effects by inhibiting the immunologically stimulated release of histamine and other proinflammatory agents from basophils 4 and skin mast cells. 5 Recently, my colleagues and I found that tacrolimus also inhibits the immunologically mediated generation of interleukin-4 from basophils. 6 These results, together with the finding that cyclosporine, which also acts on the calcium-calcineurin pathway that regulates the secretion of basophils and mast cells, 4,5 suggest that immunophilin-binding drugs are potent antiinflammatory agents.…”

Section: Tacrolimus Ointment For Atopic Dermatitismentioning

confidence: 99%

“…5 Recently, my colleagues and I found that tacrolimus also inhibits the immunologically mediated generation of interleukin-4 from basophils. 6 These results, together with the finding that cyclosporine, which also acts on the calcium-calcineurin pathway that regulates the secretion of basophils and mast cells, 4,5 suggest that immunophilin-binding drugs are potent antiinflammatory agents. 5 Therefore, although tacrolimus has remarkable properties of immunosuppression, its rapid antiinflammatory effect in patients with atopic dermatitis 1 is most likely mediated by its effects on the release of proinflammatory and vasoactive mediators from skin mast cells and infiltrating basophils.…”

Section: Tacrolimus Ointment For Atopic Dermatitismentioning

confidence: 99%

“…6 These results, together with the finding that cyclosporine, which also acts on the calcium-calcineurin pathway that regulates the secretion of basophils and mast cells, 4,5 suggest that immunophilin-binding drugs are potent antiinflammatory agents. 5 Therefore, although tacrolimus has remarkable properties of immunosuppression, its rapid antiinflammatory effect in patients with atopic dermatitis 1 is most likely mediated by its effects on the release of proinflammatory and vasoactive mediators from skin mast cells and infiltrating basophils. 2 Therefore, patients with other inflammatory skin disorders involving these cells might also benefit from treatment with these compounds.…”

Section: Tacrolimus Ointment For Atopic Dermatitismentioning

confidence: 99%

“…Tacrolimus also down-regulates the expression of the high-affinity IgE receptor on Langerhans cells and related antigen-presenting cells in the skin and inhibits their stimulatory activity in vivo. 5 One of these factors may predominate; however, it seems likely that they function synergistically in patients with atopic dermatitis. Certainly, the encouraging results of tacrolimus therapy in patients with atopic dermatitis suggest that it would be worthwhile to investigate the use of this drug in patients with other inflammatory diseases and autoimmune diseases.…”

Section: The Authors Replymentioning

confidence: 99%

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Palermo¹,

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Shackleton³

1998

N Engl J Med

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Our fax numbers: 617-739-9864 and 617-734-4457Our e-mail address: letters@nejm.orgWe cannot acknowledge receipt of your letter, but we will notify you when we have made a decision about publication. We are unable to provide prepublication proofs. Please enclose a stamped, self-addressed envelope if you want unpublished material returned to you. Financial associations or other possible conflicts of interest must be disclosed. Submission of a letter constitutes permission for the Massachusetts Medical Society, its licensees, and its assignees to use it in the Journal' s various editions (print, data base, and optical disk) and in anthologies, revisions, and any other form or medium. Correspondence Exercise-Induced AsthmaTo the Editor: In the study of long-term salmeterol treatment for exercise-induced asthma reported by Nelson et al.(July 16 issue), 1 a flaw in the procedure for selecting patients was that not all subjects were receiving concurrent therapy with inhaled corticosteroids, in accordance with asthma-management guidelines. In real life, moreover, patients normally take a b 2 -adrenergic agonist on an occasional basis before engaging in exercise.The authors state that they chose to use exercise because it is an example of a clinically relevant bronchoconstrictor stimulus. Since the inhalation of cold air augments the bronchoconstrictor response to exercise, 2 the exercise protocol they used is in effect an evaluation of two separate bronchoconstrictor stimuli. Since treatment with b 2 -adrenergic agonists is not routinely used as prophylaxis against exposure to cold air, the use of dual stimuli added confounding factors to the interpretation of the data.In their discussion, the authors do not mention the study by Simons et al. 3 This study looked at the effect of once-daily treatment with salmeterol on exercise alone in subjects who were concurrently using inhaled corticosteroids and involved an exercise challenge nine hours after the dose was given. Their study, like the study by Nelson et al., showed loss of protection after regular use.The results at 9 hours in the study by Nelson et al., like those at 6 and 12 hours in the study by Ramage et al., 4 showed that regular treatment with salmeterol provided no significant residual protection, as compared with placebo, after four weeks. These findings suggest that salmeterol should not be administered on a regular basis for exercise-induced asthma. In this respect, the use of albuterol as required before exercise would be more appropriate and cheaper. To the Editor: Nelson et al. conclude that extended administration of salmeterol "does not result in a loss of protection against clinically relevant precipitants of asthma, but the duration of action of the drug is shortened." They also state that the dissociation between salmeterol's bronchodilatory effect, which lasts for at least 12 hours, and its bronchoprotective effect, which does not last as long, "suggests an as yet undefined interaction between the stimulus and the drug." In fact, straightforward...

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Section: Exercise-induced Asthmamentioning

confidence: 75%

Section: Tacrolimus Ointment For Atopic Dermatitismentioning

confidence: 99%