Cyclosporin A and iloprost treatment of systemic sclerosis: clinical results and interleukin-6 serum changes after 12 months of therapy

Filaci, Gilberto; Cutolo, Maurizio; Scudeletti, Marco; Castagneto, Corrado; Derchi, Lorenzo E.; Gianrossi, R; Ropolo, F.; Zentilin, Patrizia; Sulli, Alberto; Murdaca, Giuseppe; Ghio, Massimo; Indiveri, Francesco; Puppo, Francesco

doi:10.1093/rheumatology/38.10.992

Cited by 86 publications

(50 citation statements)

References 26 publications

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“…An improvement of skin score after 1 year of treatment was also reported by some other studies [14,15], whereas Filaci et al, in a small group, observed improvements in skin parameters only in patients treated for 1 year with iloprost and CSA, but not in patients treated only with iloprost [16]. It is difficult to understand the significance of these changes, as longitudinal studies show that skin scores in patients with dSSc increase rapidly in the first few years and thereafter stabilise or decrease [27].…”

Section: Discussionsupporting

confidence: 79%

“…Moreover, they also offer additional information on its long-term efficacy in Raynaud's phenomenon and ischaemic ulcers, and its safety. However, data available in the literature on the longterm use of iloprost are surprisingly poor: only three small studies (each with fewer than 20 patients), with a relatively short follow-up (1 year), are available [14][15][16]. We refer here to our experience with 30 consecutive patients with SSc treated with iloprost and followed for a median of 3 years.…”

Section: Introductionmentioning

confidence: 99%

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Systemic Sclerosis Therapy with Iloprost: A Prospective Observational Study of 30 Patients Treated for a Median of 3 Years

Bettoni¹,

Geri²,

Airò³

et al. 2002

Clin Rheumatol

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Iloprost is useful in the short-term treatment of severe Raynaud's phenomenon and ischaemic ulcers in patients with systemic sclerosis (SSc), but its long-term effects are largely unknown. The aim of this study was to report long-term outcome (median follow-up 36 months) in a prospective observational study of a cohort of 30 consecutive patients with SSc who received iloprost therapy with maintenance infusions every 3 weeks after an initial cycle of 5 consecutive days. At the end of the observation, compared to the pretreatment point, we observed complete healing of digital ulcers in 19/21 patients (90%), a decrease of the Raynaud's phenomenon visual analogue score from 10/10 (25th-75th percentile 7-10) to 5/10 (4-6.75) ( P <0.001) and, in patients with diffuse cutaneous involvement, of the modified Rodnan skin thickness score from 25.5 (16.5-31.5) to 16 (13.5-20) ( P = 0.02), minimal improvement of the Health Assessment Questionnaire from 0.87 (0.68-1.37) to 0.75 (0.62-1.25), which was neither statistically nor clinically significant. The forced vital capacity was not significantly changed, but the diffusion capacity corrected for the alveolar volume decreased from 71% (54-76.7) of the expected value to 62% (51.5-71) ( P = 0.02). In one patient with limited SSc a positive effect on pulmonary hypertension was observed. Six patients, after a median of 25 months of treatment and healing of digital ulcers, discontinued the therapy; after a median of 10 months ulcers did not recur in five of these six. Other reasons for discontinuation were: tolerability (1), disease progression (normotensive renal crisis: 1), and death due to intracranial haemorrhage (1). This same patient had previously suffered a central retinal vein thrombosis. In conclusion, long-term therapy with iloprost in patients with SSc has a durable effectiveness on ischaemic ulcers and Raynaud's phenomenon, but it is not possible to conclude that the natural history of the disease was modified.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Systemic Sclerosis Therapy with Iloprost: A Prospective Observational Study of 30 Patients Treated for a Median of 3 Years

Bettoni¹,

Geri²,

Airò³

et al. 2002

Clin Rheumatol

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“…3,4 Drugs that inhibit lymphocyte activation, such as cyclosporine A, are clinically successful in the treatment of several autoimmune diseases. 5,6 T lymphocyte stimulation by mitogens, such as lectins and anti-CD3 antibodies, promotes IL-2 production and expression of IL-2 receptor. 7,8 IL-2 binds to its receptor and promotes cell proliferation by transition from G1 to S phase in the cell cycle.…”

Section: Introductionmentioning

confidence: 99%

Regulation of human lymphocyte proliferation by fatty acids

Gorjão

Cury-Boaventura

Lima

et al. 2006

Cell Biochemistry & Function

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In the present study, the effect of increasing concentrations of palmitic (PA, C16:0), stearic (SA, C18:0), oleic (OA, C18:1, n-9), linoleic (LA, C18:2n-6), docosahexaenoic (DHA, C22:6 n-3) and eicosapentaenoic (EPA, C20:5 n-3) acids on lymphocyte proliferation was investigated. The maximal non-toxic concentrations of these fatty acids for human lymphocytes in vitro were determined. It was also evaluated whether these fatty acids at non-toxic concentrations affect IL-2 induced lymphocyte proliferation and cell cycle progression. OA and LA at 25 microM increased lymphocyte proliferation and at higher concentrations (75 microM and 100 microM) inhibited it. Both fatty acids promoted cell death at 200 microM concentration. PA and SA decreased lymphocyte proliferation at 50 microM and promoted cell death at concentrations of 100 microM and above. EPA and DHA decreased lymphocyte proliferation at 25 and 50 microM being toxic at 50 and 100 microM, respectively. PA, SA, DHA and EPA decreased the stimulatory effect of IL-2 on lymphocyte proliferation, increasing the percentage of cells in G1 phase and decreasing the proportion of cells in S and G2/M phases. OA and LA caused an even greater pronounced effect. The treatment with all fatty acids increased neutral lipid accumulation in the cells but the effect was more pronounced with PA and DHA. In conclusion, PA, SA, DHA and EPA decreased lymphocyte proliferation, whereas OA and LA stimulated it at non-toxic concentrations.

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“…Так, ИЛ6 индуцирует Т-клеточную ак-тивацию и поликлональную активацию В-лимфоцитов, и это может объяснить поликлональную экспансию В-клеток и гипергаммаглобулинемию, которая нередко наблюдается при системных ревматических заболеваниях, в частности ССД [56]. Известно, что при ССД обнаруживается боль-шой спектр антиядерных и антинуклеолярных аутоанти-тел, характерных для этого заболевания, что является ос-нованием для отнесения ССД в группу аутоиммунных бо-лезней [57,58].…”

Section: Adam17unclassified

“…Средний возраст больных составил 58 (46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61) лет. Исходно 73% больных получали низкие дозы ГК (≤10 мг/сут в пересчете на преднизолон) и 57% -метотре-ксат.…”

Section: Adam17unclassified

Prospects for Using Tocilizumab in Systemic Sclerosis

Ананьева¹

2015

rsp

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Cyclosporin A and iloprost treatment of systemic sclerosis: clinical results and interleukin-6 serum changes after 12 months of therapy

Abstract: Collectively, our data suggest that the combination of low-dose CyA with iloprost administration may be of clinical utility in SSc and that a mechanism of action of CyA in SSc may include the decrease in IL-6 production.

Cited by 86 publications

References 26 publications

Systemic Sclerosis Therapy with Iloprost: A Prospective Observational Study of 30 Patients Treated for a Median of 3 Years

Systemic Sclerosis Therapy with Iloprost: A Prospective Observational Study of 30 Patients Treated for a Median of 3 Years

Regulation of human lymphocyte proliferation by fatty acids

Prospects for Using Tocilizumab in Systemic Sclerosis

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