Immunosuppressant pharmacodynamics on lymphocytes from healthy subjects and patients with chronic renal failure, nephrosis, and psoriasis: Possible implications for individual therapeutic efficacy*

Hirano, Toshihiko; Oka, Kitaro; Takeuchi, Hirohito; Kozaki, Koichi; Matsuno, Naoto; Nagao, Toshiyasu; Kozaki, M; Ichikawa, Makiko; Yoshida, Masaharu; Umezawa, Yoshinori; Hirata, Michiko; T, Ohi; Koga, Michiyuki

doi:10.1016/s0009-9236(97)90085-0

Cited by 51 publications

(77 citation statements)

References 33 publications

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“…In most cases, the drug is useful in suppressing severe clinical symptoms of AD; however, individual variations in tacrolimus efficacy, adverse effects from tacrolimus including skin burning, pruritus, varicella and blisters [40], and/or recurrence of AD after cessation of tacrolimus use have been reported. Pharmacodynamic approaches with the use of PBMCs of the patients could be an efficient strategy for the evaluation of the individual therapeutic potentials of tacrolimus, as has been shown for cyclosporine use in the treatment of psoriasis [41] and GC use in kidney transplantations [23, 41]. …”

Section: Discussionmentioning

confidence: 99%

The Role of Immune Response to <i>Staphylococcus aureus </i>Superantigens and Disease Severity in Relation to the Sensitivity to Tacrolimus in Atopic Dermatitis

Fukushima

Hirano²,

Shibayama³

et al. 2006

Int Arch Allergy Immunol

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Background:Staphylococcus aureus-producing superantigens (SAgs), such as staphylococcal enterotoxin B (SEB) or toxic shock syndrome toxin-1 (TSST-1), are frequently observed in atopic dermatitis (AD). However, little has been done to establish the association of immune responses to SAgs and the therapeutic response to immunosuppressive drugs in AD. Therefore, we investigated the prevalence and role of SAgs in the pathophysiology and immunosuppressive drug sensitivity in AD patients. Methods: We classified 29 patients into two groups on the basis of their clinical AD scores: a low-score group (n = 14) corresponding to mild to moderate patients and a high-score group (n = 15) corresponding to severe patients. We estimated the plasma anti-SEB or TSST-1 IgE of these patients and healthy subjects by ELISA. We also estimated individual drug sensitivity by determining drug concentrations that would give 50% inhibition (IC₅₀) of peripheral-blood mononuclear cell (PBMC) proliferation in vitro. Results: The levels of plasma anti-SEB or TSST-1 IgE in the severe patients were significantly higher than those in the mild to moderate patients (p < 0.05 and p < 0.01, respectively). When stimulated with concanavalin A in vitro, PBMCs in the severe patients exhibited low sensitivity to the suppressive efficacy of tacrolimus (FK506) as compared to the mild to moderate patients (p < 0.01). Furthermore, there was a significant correlation between the IC₅₀s of FK506 and plasma anti-TSST-1 IgE levels (p < 0.01). Conclusions: We showed that PBMCs in severe AD patients exhibited lower sensitivity to FK506, and had higher plasma levels of anti-TSST-1 IgE as compared to the mild AD patients. SAgs appear to be one of the causes of decreased PBMC sensitivity to FK506, and therefore an alternative treatment would be useful based on the individual drug sensitivity data and anti-TSST-1 IgE levels.

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Section: Discussionmentioning

confidence: 99%

The Role of Immune Response to <i>Staphylococcus aureus </i>Superantigens and Disease Severity in Relation to the Sensitivity to Tacrolimus in Atopic Dermatitis

Fukushima

Hirano²,

Shibayama³

et al. 2006

Int Arch Allergy Immunol

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“…This 20 ml sample size was the smallest possible to carry out the drug sensitivity tests for four immunosuppressive agents, but occasionally not all four of these agents could be tested for each subject. The heparinized blood was loaded on 3 ml of Ficoll-Hypaque (Nakarai Co., Japan), centrifuged at 1300 ×g for 20 min, and PBMCs were separated as described previously [4][5][6]21]. For the evaluation of PBMC-sensitivity to immunosuppressive drugs, cells were washed and suspended in RPMI 1640 medium containing 10% fetal bovine serum, 100,000 IU/l penicillin, and 100 mg/l streptomycin to a final density of 1× 10 6 cells/ml.…”

Section: Isolation Of Pbmcs and Evaluation Of Drug Effects In Vitromentioning

confidence: 99%

“…However, variations in the clinical efficacy of the drugs in individual patients have been observed, and patients with poor responses to the drugs have required long-term or relatively high doses and thus experience serious side effects with less improvement in their conditions [1]. One of the attractive ways to predict the clinical efficacy of immunosuppressive drugs in individual patients is the cellular pharmacodynamics of drugs using PBMCs of patient origin [4][5][6]. It has been reported that the in vitro response of PBMCs to the suppressive effects of immunosuppressive drugs correlate with clinical efficacy in asthma [7], renal transplantation [5,8], minimal change nephrotic syndrome [5,6], psoriasis [4], rheumatoid arthritis [9], and ulcerative colitis [10].…”

Section: Introductionmentioning

confidence: 99%

“…One of the attractive ways to predict the clinical efficacy of immunosuppressive drugs in individual patients is the cellular pharmacodynamics of drugs using PBMCs of patient origin [4][5][6]. It has been reported that the in vitro response of PBMCs to the suppressive effects of immunosuppressive drugs correlate with clinical efficacy in asthma [7], renal transplantation [5,8], minimal change nephrotic syndrome [5,6], psoriasis [4], rheumatoid arthritis [9], and ulcerative colitis [10]. We have also revealed a large individual differences in the PBMC-suppressive effects of glucocorticoids, cyclosporine and tacrolimus between patients, and that patients with PBMCs exhibiting poor response to the drugs in vitro also show low responses to the clinical efficacy of the drugs [4,8,11,12].…”

Section: Introductionmentioning

confidence: 99%

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Bacterial superantigen TSST-1 attenuates suppressive efficacy of glucocorticoids and calcineurin inhibitors against blastogenesis of peripheral blood mononuclear cells from patients with antineutrophil cytoplasmic antibody-associated vasculitis and nephrosis

Hirano

Fukushima

Sasaki

et al. 2006

International Immunopharmacology

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“…[1][2][3] Periodic immune monitoring using each patient's peripheral lymphocytes would be useful to individually optimize immunosuppressive drug therapy. 4,5 The lymphocyte adenosine triphosphate (ATP) assay is an in vitro diagnostic method, used to evaluate the immune status, that uses samples of whole blood stimulated with phytohemagglutinin.…”

Section: Introductionmentioning

confidence: 99%

Untitled

2014

Exp Clin Transplant

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Objectives: The adenosine triphosphate assay using peripheral lymphocytes may be useful to evaluate the risks of acute rejection and infection in kidney transplant patients. We used the adenosine triphosphate assay to evaluate differences between recipients who were treated with cyclosporine-or tacrolimus-based immunosuppressive therapy. Materials and Methods: Adenosine triphosphate levels were measured in peripheral CD4+ cells before and after transplant and were correlated with clinical outcomes in 45 kidney transplant recipients. These recipients received immunosuppressive therapy with either cyclosporine (23 patients) or tacrolimus (22 patients). Results: Adenosine triphosphate levels were significantly lower in the cyclosporine-than tacrolimus-based therapy groups from 2 to 6 weeks after transplant. Adenosine triphosphate levels were similar between these groups before and 1 week after transplant. The frequency of cytomegalovirus infection was greater in the recipients who received cyclosporine (17 patients [74%]) than tacrolimus (6 patients [27%]; P ≤ .003). The frequency of acute rejection episodes was similar between the cyclosporine and tacrolimus groups. Conclusions:These observations suggest that cyclosporine-based immunosuppressive therapy causes excessive immunosuppression compared with tacrolimus-based therapy, evidenced by the lymphocyte adenosine triphosphate levels. The adenosine triphosphate assay using peripheral CD4+ cells may be a useful method for predicting the occurrence of cytomegalovirus infections in kidney transplant recipients.

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Immunosuppressant pharmacodynamics on lymphocytes from healthy subjects and patients with chronic renal failure, nephrosis, and psoriasis: Possible implications for individual therapeutic efficacy*

Cited by 51 publications

References 33 publications

The Role of Immune Response to <i>Staphylococcus aureus </i>Superantigens and Disease Severity in Relation to the Sensitivity to Tacrolimus in Atopic Dermatitis

The Role of Immune Response to <i>Staphylococcus aureus </i>Superantigens and Disease Severity in Relation to the Sensitivity to Tacrolimus in Atopic Dermatitis

Bacterial superantigen TSST-1 attenuates suppressive efficacy of glucocorticoids and calcineurin inhibitors against blastogenesis of peripheral blood mononuclear cells from patients with antineutrophil cytoplasmic antibody-associated vasculitis and nephrosis

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