Publications by authors named "Laurindo Ferreira Da Rocha"

6 Publications

  • Page 1 of 1

Corticosteroid inhibits chemokines production in systemic sclerosis patients.

Steroids 2017 11 1;127:24-30. Epub 2017 Sep 1.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica (NUPIT), Universidade Federal de Pernambuco, Recife, PE, Brazil.

In this study, we evaluated glucocorticoids (GC) effects on cytokine/chemokine levels in serum samples and peripheral blood mononuclear cell (PBMC) production from systemic sclerosis (SSc) patients. We evaluated cytokine and chemokine levels in serum samples from SSc patients taking or not taking systemic glucocorticoids. PBMCs response to methylprednisolone (MP) was examined from 15 SSc patients and 8 healthy control subjects following PBMC stimulation with anti-CD3/CD28. Cytokine (IFN-γ, TNF, IL-2, IL-4, IL-6, IL-10, and IL-17A) and chemokine (CXCL8/IL-8, CCL5/RANTES, CXCL9/MIG, CCL2/MCP-1, and CXCL10/IP-10) levels were quantified in serum and in PBMC culture supernatants by CBA or ELISA. Compared with patients not taking corticosteroids, we did not observe any significant differences in cytokines/chemokines serum levels in patients using systemic corticosteroids. After stimulation with anti-CD3/CD28, PBMCs treated with MP (100μM), showed a significant reduction of CCL2/MCP-1 (p=0.001), CCL5/RANTES (p=0.04), and CXCL8/IL-8 (p=0.003) levels in SSc patients. In PBMC from healthy controls, we observed decreased IFN-γ, TNF, IL-2, and IL-10 levels after MP treatment, compared with stimulated condition (p<0.01 for all). However in SSc patients, we did not find any significant reduction in these cytokine levels after MP treatment. In conclusion, CCL2/MCP-1, CCL5/RANTES, and CXCL8/IL-8 are chemokines that are potentially modulated by corticosteroids in vitro in SSc patients, but no effect was observed on IL-2, IL-4, IL-6, IL-10, IL-17A, TFN, and IFN-γ secretion. These results suggest a potential effect of GCs on SSc treatment and may reflect the benefit of their use in some patients.
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http://dx.doi.org/10.1016/j.steroids.2017.08.012DOI Listing
November 2017

The Role of PPAR Gamma in Systemic Sclerosis.

PPAR Res 2015 6;2015:124624. Epub 2015 May 6.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas da Universidade Federal de Pernambuco (LINAT-UFPE), 50670-901 Recife, PE, Brazil.

Fibrosis is recognized as an important feature of many chronic diseases, such as systemic sclerosis (SSc), an autoimmune disease of unknown etiology, characterized by immune dysregulation and vascular injury, followed by progressive fibrosis affecting the skin and multiple internal organs. SSc has a poor prognosis because no therapy has been shown to reverse or arrest the progression of fibrosis, representing a major unmet medical need. Recently, antifibrotic effects of PPARγ ligands have been studied in vitro and in vivo and some theories have emerged leading to new insights. Aberrant PPARγ function seems to be implicated in pathological fibrosis in the skin and lungs. This antifibrotic effect is mainly related to the inhibition of TGF-β/Smad signal transduction but other pathways can be involved. This review focused on recent studies that identified PPARγ as an important novel pathway with critical roles in regulating connective tissue homeostasis, with emphasis on skin and lung fibrosis and its role on systemic sclerosis.
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http://dx.doi.org/10.1155/2015/124624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438188PMC
June 2015

Simvastatin inhibits cytokines in a dose response in patients with rheumatoid arthritis.

Inflamm Res 2014 Apr 14;63(4):309-15. Epub 2014 Jan 14.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino, Recife, Brazil.

Objective And Design: To evaluate the effects of simvastatin in peripheral blood mononuclear cell (PBMC) cytokines profiles and correlate with the disease state of rheumatoid arthritis (RA) patients.

Methods: The PBMC from 22 RA patients were purified and stimulated or not stimulated with phorbol myristate acetate/ionomycin and were treated with simvastatin in different doses. Cytokine levels were quantified by ELISA and patients were assessed for clinical and laboratory variables. This assessment included disease activity measures [Clinical Disease Activity Index (CDAI), Disease Activity Score for 28 joints (DAS28)] and a Health Assessment Questionnaire.

Results: The IL-17A, IL-6, IL-22 and IFN-γ were significantly reduced in a dose response after simvastatin treatment (50 μM, p = 0.0005; p < 0.0001; p < 0.02; p = 0.0005, respectively). The IL-17A and IL-6 cytokines were also significantly reduced in lower concentrations of simvastatin (10 μM) compared to controls (p = 0.018; p = 0.04) and compared to the standard drug (p = 0.007; p = 0.0001). The results also showed that only RA patients with severe disease (DAS28 >5.1 and CDAI >22) had poor response to simvastatin in reducing cytokines levels, mainly for IL-17A and IL-22 cytokines (p = 0.03; p = 0.039, respectively).

Conclusion: The RA patients in clinical remission, mild or moderate had lower levels of all cytokines analyzed after simvastatin treatment, showing that these patients have better response to treatment. Our findings suggest that the simvastatin therapy modulates different cytokines in a dose dependent manner and its effect is associated with stratification of patients according to disease activity.
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http://dx.doi.org/10.1007/s00011-013-0702-4DOI Listing
April 2014

Hydroxychloroquine decreases Th17-related cytokines in systemic lupus erythematosus and rheumatoid arthritis patients.

Clinics (Sao Paulo) 2013 Jun;68(6):766-71

Universidade Federal de Pernambuco, Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Recife/PE, Brasil.

Objectives: Hydroxychloroquine is an antimalarial agent that has been used in systemic lupus erythematosus and rheumatoid arthritis treatment for many years. Recently, novel mechanisms of action have been proposed, thereby broadening the therapeutic perspective of this medication. The purpose of this study was to evaluate the immunomodulatory activity of hydroxychloroquine in T helper 17 (Th17) cytokines in healthy individuals and patients.

Methods: Eighteen female patients with systemic lupus erythematosus (mean age 39.0±12.9 years) and 13 female patients with rheumatoid arthritis (mean age 51.5±7.7 years) were recruited from Universidade Federal de Pernambuco-Brazil. The patients were included after fulfilling four classification criteria for systemic lupus erythematosus or rheumatoid arthritis from the American College of Rheumatology. After being stimulated with phorbol 12-myristate 13-acetate and ionomycin in the absence or presence of different concentrations of hydroxychloroquine, the interleukin 6, 17 and 22 levels were quantified with an enzyme-linked immunosorbent assay in culture supernatants of peripheral blood mononuclear cells from healthy individuals and patients.

Results: We demonstrated that in peripheral blood mononuclear cells from healthy volunteers and in systemic lupus erythematosus and rheumatoid arthritis patients, there was a significant reduction in the IL-6, IL-17 and IL-22 supernatant levels after adding hydroxychloroquine. CONCLUSIONS Our in vitro results demonstrated that hydroxychloroquine inhibits IL-6, IL-17 and IL-22 production and contributes to a better understanding of the mechanism of action of this medication.
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http://dx.doi.org/10.6061/clinics/2013(06)07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674253PMC
June 2013

Decreased serum interleukin 27 in Brazilian systemic lupus erythematosus patients.

Mol Biol Rep 2013 Aug 6;40(8):4889-92. Epub 2013 May 6.

Hospital das Clínicas, Universidade Federal de Pernambuco, Recife, PE, Brazil.

The immunological role of interleukin 27 has been reported in various inflammatory diseases, but its importance in systemic lupus erythematosus pathogenesis is not completely established. The aim of this study was to evaluate serum levels of IL-27 in SLE patients and its correlation with clinical manifestations and disease activity. IL-27 levels were assessed in 70 SLE patients and 30 healthy controls by ELISA. Clinical and laboratory parameters were recorded. Statistic analyzes were performed by Graph Prism 3.02 software. The IL-27 serum levels were significantly decreased in SLE patients compared with controls (mean 899.92 and 1,531.22 pg/ml, P=0.0005). There was a correlation between IL-27 levels and C3 levels (P=0.004). Nevertheless, there was no association of serum IL-27 levels with disease activity evaluated by SLEDAI score (P=0.9605). No significant difference was found regarding IL-27 levels between SLE patients with and without nephritis, haematuria, proteinuria and positive anti-dsDNA. Correlation analysis between serum IL-27 levels and SLEDAI, SLICC, proteinuria levels, C4 and CH50 levels also showed no association. These data demonstrated decreased serum levels of IL-27 in SLE patients but further studies are needed to clarify the precise role of this cytokine and its potential use as therapeutic target.
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http://dx.doi.org/10.1007/s11033-013-2588-1DOI Listing
August 2013

Increased serum interleukin 22 in patients with rheumatoid arthritis and correlation with disease activity.

J Rheumatol 2012 Jul 15;39(7):1320-5. Epub 2012 May 15.

Universidade Federal de Pernambuco (UFPE), Recife, Brazil.

Objective: To analyze the role of interleukin 22 (IL-22) in rheumatoid arthritis (RA).

Methods: IL-22 serum levels were measured in 83 patients with established RA under treatment with disease-modifying antirheumatic drugs and in 30 healthy controls matched for age and sex. Patients were assessed for clinical and laboratory variables. Correlations of IL-22 serum levels with disease activity measures [Clinical Disease Activity Index (CDAI) and Disease Activity Score for 28 joints (DAS28)], serological markers, bone erosions, and demographic factors were assessed. Peripheral blood mononuclear cells (PBMC) from 30 patients with RA and 14 controls were purified and stimulated in vitro with phorbol myristate acetate (PMA)/ionomycin. IL-22 production by PBMC and in serum was investigated by ELISA.

Results: IL-22 levels were increased in patients with RA compared with controls (mean 432.37 pg/ml and 67.45 pg/ml, respectively; p < 0.001). Levels of IL-22 correlated with DAS28 and CDAI measures. Rheumatoid factor (RF) positivity was correlated with higher levels of IL-22 in patients with RA (mean 575.08 pg/ml; p = 0.001). The presence of bone erosions was associated with high IL-22 levels (p = 0.0001). PBMC stimulated with PMA/ionomycin expressed higher levels of IL-22 in patients with RA than controls but this was not significant (mean 584.75 pg/ml and 295.57 pg/ml; p = 0.553).

Conclusion: IL-22 is elevated in the serum of patients with established RA. Elevated serum IL-22 allows discrimination between patients with different clinical and laboratory measures and indicates the potential of IL-22 as an additional tool for assessment of activity in RA, particularly in patients with RF antibodies and longterm disease. IL-22 is associated with bone-destructive disease.
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http://dx.doi.org/10.3899/jrheum.111027DOI Listing
July 2012
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