Effect of immunosuppressive agents FK506 and cyclosporin and steroids on the expression of IL-6 and its receptor by stimulated lymphocytes and monocytes

Moutabarrik, A; Hachim, Khadija; Bengahnem, M. G.; Ramadani, Benyounes; Zaïd, D; Nakanishi, Isao; Takahara, Shiro; Ishibashi, M

doi:10.1111/j.1432-2277.1994.tb01441.x

Cited by 7 publications

(7 citation statements)

References 4 publications

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“…Both in undiffe re ntiate d and diffe re ntiate d U937 ce lls, at the highest conce ntration use d use d (200 ng/mL) CsA dec reased stimulate d se cretion of IL-6, more than 50%, a value similar to that reporte d by Moutbarrik e t a l. 26 In human monocytes at therapeutic c oncentrations in v ivo . Additionally, CsA decre ased the intrac e llular conc entratio n of IL-6.…”

Section: Effect Of Csa On Interleukin-6 Productionsupporting

confidence: 76%

Cyclosporin A Decreases Human Macrophage Interleukin‐6 Synthesis at Post‐Transcriptional Level

García

Lopez

Cabo³

et al. 1999

Mediators of Inflammation

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In addition to its well-established effect on T cells, cyclosporin A (CsA) also inhibits inflammatory cytokine production by macrophages. However, little is known about the mechanism of action of CsA on macrophage cytokine production. We measured the effect of CsA on basal and phorbol-myristate-acetate (PMA)-stimulated production of interleukin-6 using the human monocyte cell line U937 differentiated with dimethylsulfoxide (DMSO). Interleukin-6 levels were measured in supernatant and cell lysates using specific enzyme-linked immunosorbent assays. We found that CsA decreases not only IL-6 release but also cytokine synthesis. The concentration of CsA used did not affect either cell viability or proliferation. Three possibilities may be advanced to explain the CsA-due decrease in IL-6 production by macrophages: (a) inhibition of the synthesis of an early common regulatory protein, (b) inhibition of cytokine gene transcription, or (c) modulation of post-transcriptional events. The first possibility was tested by measuring the effect of cycloheximide on the experimental system during the first 3 hours of culture. Although cycloheximide decreased total cytokine synthesis, the pattern of cytokine modulation by CsA persisted. These data suggest that CsA-mediated macrophage cytokine inhibition is not mediated by an early common regulatory protein. To further explore the inhibition mechanism, we measured IL-6 mRNA levels by Northern blot. IL-6 mRNA levels were unaffected by CsA both in resting and PMA-stimulated cells. We conclude that in human macrophages CsA diminishes IL-6 production at post-transcriptional level.

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Section: Effect Of Csa On Interleukin-6 Productionsupporting

confidence: 76%

Cyclosporin A Decreases Human Macrophage Interleukin‐6 Synthesis at Post‐Transcriptional Level

García

Lopez

Cabo³

et al. 1999

Mediators of Inflammation

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“…The reduction in the cytokine level might be linked to starting immunosuppressive treatment like CYA and tacrolimus, which can downregulate IL-6 expression. 18 Why this decrease is not confirmed at 6 months and 1 year is unclear but this might be related to a loss of statistical power as a result of a lower number of paired samples as the study went by. IL-8 is a key chemoattractant for neutrophils and its sputum level was repeatedly shown to be increased in a series of neutrophilic airway diseases such as COPD, cystic fibrosis and bronchiectasis.…”

Section: Discussionmentioning

confidence: 96%

Sputum cytokine levels in patients undergoing hematopoietic SCT and comparison with healthy subjects and COPD: a pilot study

Moermans

Bonnet

Willems

et al. 2014

Bone Marrow Transplant

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Patients undergoing hematopoietic SCT (HSCT) display an airway neutrophilic inflammation before transplantation that persists over the years. In this study, we have investigated the cytokine profile over a period of 1 year in the sputum supernatant of patients who underwent HSCT. We have measured sputum supernatant levels of TNF-α, TGF-β1, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17 and IFN-γ in 49 HSCT patients and compared the results with those found in 40 chronic obstructive pulmonary disease (COPD) and 54 healthy subjects matched for age. Compared with healthy subjects, before transplantation, HSCT patients exhibited raised levels of IL-6 (P o0.001) and IL-8 (P o 0.05) while the other cytokines were generally poorly detectable. This picture was rather similar to that seen in COPD even if cytokine levels were much greater in the latter, with IL-8 being significantly greater in COPD than in HSCT patients (P o0.0001). In the 1 year following transplantation, sputum IL-6 and IL-8 did not differ from those in healthy subjects. Overall in HSCT patients, sputum IL-8 and IL-6 correlated with sputum neutrophil counts (r = 0.4, P o 0.0001; r = 0.42, P o 0.0001, respectively). In conclusion, sputum IL-6 and IL-8 may play a role in neutrophilic airway inflammation seen in patients undergoing HSCT.

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“…These results suggest further that there may be elements downstream of IL‐6 that can interact directly and/or indirectly with the promoter region of the ATP2A2 and ATP2C1 genes. In addition, steroids, ciclosporin A and FK‐506 at immunosuppressive concentrations induced a dose‐dependent inhibition of IL‐6 secretion from various cells 31 . Furthermore, it is thought that in the inflammation phase of DD and HHD, the effects of several curatives are carried by upregulation of expression in both genes through the inhibition of IL‐6 production or else these direct promotion for sufficient increase in mRNA levels.…”

Section: Discussionmentioning

confidence: 99%

Effects of drugs and anticytokine antibodies on expression of ATP2A2 and ATP2C1 in cultured normal human keratinocytes

et al. 2005

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Effect of immunosuppressive agents FK506 and cyclosporin and steroids on the expression of IL-6 and its receptor by stimulated lymphocytes and monocytes

Cited by 7 publications

References 4 publications

Cyclosporin A Decreases Human Macrophage Interleukin‐6 Synthesis at Post‐Transcriptional Level

Cyclosporin A Decreases Human Macrophage Interleukin‐6 Synthesis at Post‐Transcriptional Level

Sputum cytokine levels in patients undergoing hematopoietic SCT and comparison with healthy subjects and COPD: a pilot study

Effects of drugs and anticytokine antibodies on expression of ATP2A2 and ATP2C1 in cultured normal human keratinocytes

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