Iloprost treatment reduces TNF-alpha production and TNF-RII expression in critical limb ischemia patients without affecting IL6

Renzo, M. Di; Pieragalli, D.; Meini, Simone; Franco, V. De; Pompella, Gerarda; Auteri, Alberto; Pasqui, Anna Laura

doi:10.1016/j.plefa.2005.05.025

Cited by 18 publications

(11 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It coordinates the production of genes that control cellular growth and inflammation and decreases productions of cytokines in vitro. In addition to its vasodilatator and antiaggregating effects, it may also has anti-inflammatory properties 33 . Iloprost can be administrated as through inhalational route or by intravenous infusion 34 .…”

Section: Histopathological Resultsmentioning

confidence: 99%

Iloprost reduces colonic injury in ischemic colitis in rats

Karatepe¹,

Cakir²,

Ünal³

et al. 2011

Acta Cir. Bras.

View full text Add to dashboard Cite

Purpose: Evaluate the effects of iloprost administration in the early period of ischemic colitis and the mechanism that how these effects develop. Methods: Thirty two Wistar albino female rats with an average weight of 220g were divided into four groups of eight rats. In group 1 the rats were given iloprost and sacrificed after 24 hours and in group 2 they were sacrificed after 24 hours without any iloprost. The rats in group 3 were administrated iloprost and sacrificed after 72 hours and in group 4 they were sacrificed at 72 th hour without iloprost. The differences between the groups as tissue damage, vascularization or apoptosis were assessed statistically. Results: Oxidative damage and apoptosis were less pronounced and vascularization was better developed in rats that were given iloprost and sacrificed at 24 th hour later in contrast to the rats that were not treated with iloprost. But there was no statistical difference among the groups at 72 th hour. Conclusion: Iloprost inhibited leucocyte infiltration, decreased proinflammatory cytokines and enhanced angiogenesis so that the oxidative stress and inflammatory response decreased resulting in lesser tissue damage. Key words: Colitis, Ischemic. Iloprost. Epoprostenol. Arachidonic Acid. Prostaglandins. Rats. RESUMOObjetivo: Avaliar os efeitos da administração de iloprosta no período precoce da colite isquêmica e o mecanismo da evolução destes efeitos. Métodos: Trinta e dois ratos Wistar fêmeas em torno de 220g foram distribuídos em quatro grupos de oito ratos. No grupo 1 administração de iloprosta e sacrificados após 24 horas; no grupo 2 foram sacrificados após 24 horas sem iloprosta; no grupo 3 foi administrado iloprosta e sacrificados após 72 horas; no grupo 4 foram sacrificados após 72 horas sem Iloprosta. As diferenças entre os grupos no referente a dano tecidual. vascularização ou apoptose foi apurada estatisticamente. Resultados: Dano oxidativo e apoptose foram menos acentuados e a vascularização foi melhor nos ratos que receberam iloprosta e sacrificados após 24 horas em contraste com os ratos que não receberam iloprosta. Porém, não houve diferença estatisticamente significante entre os grupos de 72 horas. Conclusão: Iloprosta inibe infiltração leucocitária, diminui a ação inflamatória de citoquinas e estimula angiogênese resultando em menor dano tecidual. Descritores: Colite Isquêmica. Iloprosta. Epoprostenol. Ácido Araquidônico. Prostaglandinas. Ratos.

show abstract

Section: Histopathological Resultsmentioning

confidence: 99%

Iloprost reduces colonic injury in ischemic colitis in rats

Karatepe¹,

Cakir²,

Ünal³

et al. 2011

Acta Cir. Bras.

View full text Add to dashboard Cite

show abstract

“…PGI 2 is now known to be a powerful cardiovascular protective agent with wide-ranging anti-inflammatory actions (11, 15–17, 19, 21, 43–45), yet few details are known as to how this agent combats proinflammatory cytokine generation at the transcriptional level (20, 46, 47, 49). For the first time our data define detailed transcriptional mechanisms by which PGI 2 inhibits MCP-1 production via the critical cardiovascular inflammatory axis of IFN-γ-STAT1 in monocytes.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to its vasodilator effects, there is now evidence suggesting PGI 2 also benefits PAH patients via anti-inflammatory actions (15). Importantly, PGI 2 has been demonstrated to exhibit anti-inflammatory actions in asthma models in vivo (16, 17), in diabetic patients with vascular inflammation (18), in critical limb ischemia (19), and bacterial inflammation in vitro (20, 21). Its use is reported to reduce the elevated circulating levels of the cytokine monocyte chemoattractant protein MCP-1 (CCL2) found in PAH patients (15).…”

Section: Introductionmentioning

confidence: 99%

“…The goal of this study was to determine the signaling pathways through which PGI 2 inhibits cytokine production in monocytes (15–17, 19–21). As an approach we investigated the effects of PGI 2 on IFN-γ-stimulated MCP-1 production in monocytes, as this signaling cascade is fairly well characterized, and appears to be one of the principle means utilized to generate vascular inflammation sand MCP-1 in vivo (3, 29, 30).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prostacyclin Inhibits IFN-γ-Stimulated Cytokine Expression by Reduced Recruitment of CBP/p300 to STAT1 in a SOCS-1-Independent Manner

Strassheim

Riddle

Burke

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

Increasing evidence indicates that pulmonary arterial hypertension is a vascular inflammatory disease. Prostacyclin (PGI2) is widely used to treat pulmonary arterial hypertension and is believed to benefit patients largely through vasodilatory effects. PGI2 is also increasingly believed to have anti-inflammatory effects, including decreasing leukocyte cytokine production, yet few mechanistic details exist to explain how these effects are mediated at the transcriptional level. Because activated monocytes are critical sources of MCP-1 and other cytokines in cardiovascular inflammation, we examined the effects of iloprost on IFN-γ- and IL-6-stimulated cytokine production in human monocytes. We found that iloprost inhibited IFN-γ- and IL-6-induced MCP-1, IL-8, RANTES, and TNF-α production in monocytes, indicating wide-ranging anti-inflammatory action. We found that activation of STAT1 was critical for IFN-γ-induced MCP-1 production and demonstrated that iloprost inhibited STAT1 activation by several actions as follows: 1) iloprost inhibited the phosphorylation of STAT1-S727 in the transactivation domain, thereby reducing recruitment of the histone acetylase and coactivator CBP/p300 to STAT1; 2) iloprost selectively inhibited activation of JAK2 but not JAK1, both responsible for activation of STAT1 via phosphorylation of STAT1-Y701, resulting in reduced nuclear recruitment and activation of STAT1; and 3) SOCS-1, which normally terminates IFN-γ-signaling, was not involved in iloprost-mediated inhibition of STAT1, indicating divergence from the classical pathway for terminating IFN-γ-signaling. We conclude that PGI2 exerts anti-inflammatory action by inhibiting STAT1-induced cytokine production, in part by targeting the transactivation domain-induced recruitment of the histone acetylase CBP/p300.

show abstract

“…Of the two studies in humans [21,22], only Filaci et al [22] evaluated the effect of iloprost in SSc. Its potential in this disease is thus an open question.…”

Section: Introductionmentioning

confidence: 99%

Iloprost modulates the immune response in systemic sclerosis

et al. 2010

View full text Add to dashboard Cite

BackgroundIloprost has been suggested to possess anti-inflammatory and immunomodulating actions and it is widely use as a vasodilatator in systemic sclerosis (SSc). In this study we evaluate the effect of iloprost on immune response in SSc patients. To this extend we enrolled 15 women affected by SSc and infused iloprost for 5 days. The effect of iloprost on T cells and monocytes was measured by flow cytometry, Real time PCR and measuring cytokines production in vivo and in vitro by ELISA.ResultsOur results demonstrate that Iloprost reduces T cell and TNF alpha production both in vivo and in vitro. It reduces T regulatory cells number, but increases their activity after immune stimulation. It increases serum IL-2 and this increase persists 28 days after the last infusion, also RANKL was increased both in vivo and in vitro. We observed no effect on IFN gamma production.ConclusionsThese results suggest that iloprost has anti-inflammatory and immunomodulating effects, reducing TNF alpha production by T cells and the number of T regulatory cells and increasing IL-2 and RANKL.

show abstract

Iloprost treatment reduces TNF-alpha production and TNF-RII expression in critical limb ischemia patients without affecting IL6

Cited by 18 publications

References 22 publications

Iloprost reduces colonic injury in ischemic colitis in rats

Iloprost reduces colonic injury in ischemic colitis in rats

Prostacyclin Inhibits IFN-γ-Stimulated Cytokine Expression by Reduced Recruitment of CBP/p300 to STAT1 in a SOCS-1-Independent Manner

Iloprost modulates the immune response in systemic sclerosis

Contact Info

Product

Resources

About