Effect of cyclosporin A on inflammatory cytokine production by human alveolar macrophages

García, Juan Emilio Losa; Rodríguez, Fernando Mateos; López, Antonio Jiménez; Salgado, Moses; Cabo, María Rosa Martín de; Pérez-Losada, Jesús; Arellano, Jose Luis Pérez

doi:10.1016/s0954-6111(98)90002-6

Cited by 49 publications

(18 citation statements)

References 23 publications

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“…The mechanisms of this undesirable effect of FK506 are unknown. However, with respect to CsA, it has been shown to induce the production of pro-inflammatory cytokines in human airway epithelial cells in a dose-dependent manner [27], although other studies have indicated that CsA has inhibitory effects on the release of pro-inflammatory mediators and has T-lymphocyte-associated immunosuppressive actions [12]. These findings of acute injury phase could implicate that individuals who chronically receive FK506 as an immunosuppressive drug may be at greater risk for acute-lung injury and permeability-pulmonary oedema.…”

Section: Discussionmentioning

confidence: 99%

“…FK506 is known to exhibit its pharmacological effects on inflammatory cells, including T-cells, macrophages [12], eosinophils [16] and neutrophils [17]. Little is known regarding the effect of FK506 on fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that calcineurin inhibitors inhibit the release of pro-inflammatory mediators in addition to possessing T-lymphocyte-associated immunosuppressive activity [12]. Therefore, continuous FK506 treatment initiated at the acute BLM injury phase would be expected to result in decreased fibrosis in the BLM model.…”

Section: Effect Of Early Fk506 Treatment In Blm Micementioning

confidence: 99%

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Use of tacrolimus, a potent antifibrotic agent, in bleomycin-induced lung fibrosis

Nagano¹

2006

Eur Respir J

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Idiopathic pulmonary fibrosis has a poor prognosis and few efficacious treatments. The immunosuppressant cyclosporin A has been shown to inhibit tumour growth factor (TGF)-binduced collagen deposition in vitro, and is widely used in Japan as a potent antifibrotic agent. Tacrolimus (FK506) is another attractive immunosuppressant, which may be useful in the treatment of pulmonary fibrosis. The aim of the present study was to elucidate the antifibrotic effect of FK506.The inhibitory effect of FK506 on collagen synthesis in cultured lung fibroblastic cells, TIG-3-20, and its antifibrotic effect on bleomycin (BLM)-induced pulmonary fibrosis in mice was investigated.FK506 inhibited TGF-b-induced collagen synthesis, and suppressed the expression of TGF-b type I receptor (TbR-I) in TIG-3-20 cells. Consistent with the in vitro findings, FK506 treatment starting on day 6 attenuated BLM-induced pulmonary fibrosis, in part, via reduced TbR-I expression. FK506 treatment in the acute BLM injury phase unexpectedly increased proinflammatory cytokine levels in bronchoalveolar lavage fluid and enhanced lung injury, resulting in poor survival.In conclusion, the present results suggest that FK506 has a potent antifibrotic effect and may be useful for the treatment of pulmonary fibrosis, although its use in the acute inflammatory phase may exacerbate lung injury.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Effect Of Early Fk506 Treatment In Blm Micementioning

confidence: 99%

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Use of tacrolimus, a potent antifibrotic agent, in bleomycin-induced lung fibrosis

Nagano¹

2006

Eur Respir J

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“…CsA is an immunomodulatory drug that plays a role in inhibiting the activation of helper T cells and alveolar macrophages (14), and has been used to treat several types of pulmonary interstitial diseases (15)(16)(17). The pathogenesis of OP remains speculative.…”

Section: Discussionmentioning

confidence: 99%

Adjunctive Effects of Cyclosporine and Macrolide in Rapidly Progressive Cryptogenic Organizing Pneumonia with no Prompt Response to Steroid

et al. 2011

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Cryptogenic organizing pneumonia (COP) generally responds well to corticosteroids with a favorable outcome. However, it can rapidly worsen and lead to respiratory failure that is refractory to corticosteroids. Adjunctive drugs have been used in refractory cases with various outcomes, but treatment experience is still lacking. We present a case of rapidly progressive COP accompanying air leak syndrome, which showed no prompt response to corticosteroids alone but gradual improvement with the addition of cyclosporine and macrolide. This case report supports the existing literature suggesting that an early therapeutic trial of this drug combination might be considered in COP patients whose condition worsens despite corticosteroid administration.

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“…CsA was shown to block mitogen-induced production of the chemokines, IL-8 and IP-10, by human T cells (24), but had no effect on LPS-induced IL-8 production by human monocytes (25) and only modestly decreased production of IL-8 by LPS-treated alveolar macrophages (26). In contrast, CsA enhanced IL-1β-induced fibroblast production of IL-8 but decreased associated production of MCP-1 (27).…”

Section: Figurementioning

confidence: 98%

Targeting of the chemokine receptor CCR1 suppresses development of acute and chronic cardiac allograft rejection

Gao¹,

Topham²,

King³

et al. 2000

J. Clin. Invest.

236

148

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IntroductionMononuclear cell recruitment to an allograft is a classic hallmark of cellular rejection. At least in broad terms, such leukocyte recruitment from the vascular pool across activated endothelial cells and into tissues is now reasonably well understood (1). Thus, leukocytes roll along selectin-expressing endothelium adjacent to a chemoattractant source, attach more firmly, change shape, migrate between adjacent endothelial cells as a result of integrin and other adhesion molecule binding, and migrate through extravascular tissues along chemotactic gradients to reach their destination. The latter chemokine/chemokine receptor phase is the least understood, with little in vivo data available. However, given the burgeoning field of chemokine biology, dissecting which molecules are generated in a given inflammatory setting, and especially the nature of chemokine receptors responsible for leukocyte recruitment, might well prove key to developing better therapeutic strategies for the prevention and treatment of allograft rejection. The current literature on chemokine receptor expression in organ transplants is limited to 2 papers noting expression of CXCR4 (ref. The current studies involve serial analysis of intragraft chemokine and chemokine receptor expression within completely MHC-mismatched mouse cardiac allografts. On the basis of our initial data, in which several chemokine receptors and their ligands were associated with host mononuclear cell infiltration, we undertook a detailed analysis of the significance of 1 of the more highly expressed chemokine receptors, CCR1 (4), which binds RANTES, macrophage inflammatory protein 1-alpha (MIP-1α), and various monocyte chemoattractant proteins (MCPs). Our studies demonstrate that compared with control CCR1 +/+ mice, CCR1 -/-mice show significantly delayed, or in some cases an absence of, acute or chronic rejection, such that targeting of CCR1 may eventually prove of therapeutic significance clinically. Although mononuclear cell infiltration is a hallmark of cellular rejection of a vascularized allograft, efforts to inhibit rejection by blocking leukocyte-endothelial cell adhesion have proved largely unsuccessful, perhaps in part because of persistent generation of chemokines within rejecting grafts. We now provide, to our knowledge, the first evidence that in vivo blockade of specific chemokine receptors is of therapeutic significance in organ transplantation. Inbred mice with a targeted deletion of the chemokine receptor CCR1 showed significant prolongation of allograft survival in 4 models. First, cardiac allografts across a class II mismatch were rejected by CCR1 +/+ recipients but were accepted permanently by CCR1 -/-recipients. Second, CCR1 -/-mice rejected completely class I-and class II-mismatched BALB/c cardiac allografts more slowly than control mice. Third, levels of cyclosporin A that had marginal effects in CCR1 +/+ mice resulted in permanent allograft acceptance in CCR1 -/-recipients. These latter allografts showed no sign of chronic rejection 50-...

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Effect of cyclosporin A on inflammatory cytokine production by human alveolar macrophages

Cited by 49 publications

References 23 publications

Use of tacrolimus, a potent antifibrotic agent, in bleomycin-induced lung fibrosis

Use of tacrolimus, a potent antifibrotic agent, in bleomycin-induced lung fibrosis

Adjunctive Effects of Cyclosporine and Macrolide in Rapidly Progressive Cryptogenic Organizing Pneumonia with no Prompt Response to Steroid

Targeting of the chemokine receptor CCR1 suppresses development of acute and chronic cardiac allograft rejection

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