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Differential expression of pro-inflammatory cytokines IL-15Ralpha, IL-15, IL-6 and TNFalpha in synovial fluid from rheumatoid arthritis patients.

Santos Savio A, Machado Diaz AC, Chico Capote A, Miranda Navarro J, Rodríguez Alvarez Y, Bringas Pérez R, Estévez del Toro M, Guillen Nieto GE - BMC Musculoskelet Disord (2015)

Bottom Line: We found higher and significant levels of TNFalpha, IL-6 and IL-15Ralpha but not of IL-15 in RA compared with the OA group.In addition we found correlation between the value of IL-15Ralpha in SF and disease activity score, DAS28.Finally, we found a correlation between IL-15Ralpha-IL-6, IL-15Ralpha-IL-15, but we did not find any correlation between other pairs of studied cytokines in SF.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutical Division, Center for Genetic Engineering and Biotechnology, Havana, CP 10600, Cuba. alicia.santos@cigb.edu.cu.

ABSTRACT

Background: Pro-inflammatory cytokines are directly implicated in the pathogenesis of Rheumatoid arthritis (RA). Variable clinical response to cytokine targeted therapies as TNFalpha and IL-6, strongly highlights the heterogeneity of inflammatory process in RA. Another cytokine, IL-15 has also been related to the inflammatory process in RA. Recently we described for the first time, the presence of its specific receptor, IL-15Ralpha, in synovial fluid (SF). The aim of this work was to compare the expression profile of IL-15Ralpha, its ligand IL-15, TNFalpha and IL-6 and how these cytokines are correlated in SF from RA patients taking as a reference Osteoarthritis (OA), an articular but not autoimmune disease.

Methods: Synovial fluids were obtained from the knee joints of 60 patients, 30 with confirmed diagnosis of RA and 30 with OA diagnosis. The levels of TNFalpha, IL-6, IL-15 and IL-15Ralpha were measured by ELISA. A statistical analysis was performed with GraphPad Prism v5.0 using the Mann-Whitney U test and Spearman's rank correlation. A cluster analysis was run in MeV software v4.9.0 and differences across clusters were evaluated by an ANOVA including post-test analysis.

Results: We found higher and significant levels of TNFalpha, IL-6 and IL-15Ralpha but not of IL-15 in RA compared with the OA group. Additionally, a high inter-individual variability in the levels of these 4 cytokines was observed in RA, although we identified 4 patients' subgroups by cluster analysis of cytokines concentration in SF. We also found a positive correlation between IL-15Ralpha-IL-6 and IL-15Ralpha-IL-15, but not for other pairs of cytokines in RA. In addition we found correlation between the value of IL-15Ralpha in SF and disease activity score, DAS28.

Conclusions: In our current work we found a high inter-individual variability in the levels of TNFalpha, IL-6, IL-15 and IL-15Ralpha in SF of RA patients and were identified four principal clusters of cytokines concentration in SF, suggesting the importance of identifying disease subset of patients for personalized treatment. Finally, we found a correlation between IL-15Ralpha-IL-6, IL-15Ralpha-IL-15, but we did not find any correlation between other pairs of studied cytokines in SF.

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Measured levels of sIL-15Ralpha, IL-15, IL-6 and TNFalpha in synovial fluids from RA and OA patients. Cytokine concentration of IL-15Ralpha (A), IL-15 (B), TNFalpha (C) and IL-6 (D) were measured in in duplicate SF samples from RA (n = 30) and OA (n = 30) by ELISA. Box plot represents media ± SD. Differences between two groups were performed by Mann–Whitney U test for nonparametric data.
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Fig1: Measured levels of sIL-15Ralpha, IL-15, IL-6 and TNFalpha in synovial fluids from RA and OA patients. Cytokine concentration of IL-15Ralpha (A), IL-15 (B), TNFalpha (C) and IL-6 (D) were measured in in duplicate SF samples from RA (n = 30) and OA (n = 30) by ELISA. Box plot represents media ± SD. Differences between two groups were performed by Mann–Whitney U test for nonparametric data.

Mentions: Quantification by ELISA of cytokines IL-15Ralpha, IL-15, IL-6, and TNFalpha in synovial fluids from the knee joints of 30 RA and 29 OA patients, showed that SF from RA patients contained significantly higher concentrations of IL-15Ralpha (p = 0.03, Figure 1A), TNFalpha (p = 0.002, Figure 1C) and IL-6 (p = 0.001, Figure 1D) than the OA group, but in the case of IL-15 we did not find any significant difference between RA and OA groups (p = 0.29) (Figure 1B).Figure 1


Differential expression of pro-inflammatory cytokines IL-15Ralpha, IL-15, IL-6 and TNFalpha in synovial fluid from rheumatoid arthritis patients.

Santos Savio A, Machado Diaz AC, Chico Capote A, Miranda Navarro J, Rodríguez Alvarez Y, Bringas Pérez R, Estévez del Toro M, Guillen Nieto GE - BMC Musculoskelet Disord (2015)

Measured levels of sIL-15Ralpha, IL-15, IL-6 and TNFalpha in synovial fluids from RA and OA patients. Cytokine concentration of IL-15Ralpha (A), IL-15 (B), TNFalpha (C) and IL-6 (D) were measured in in duplicate SF samples from RA (n = 30) and OA (n = 30) by ELISA. Box plot represents media ± SD. Differences between two groups were performed by Mann–Whitney U test for nonparametric data.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4359511&req=5

Fig1: Measured levels of sIL-15Ralpha, IL-15, IL-6 and TNFalpha in synovial fluids from RA and OA patients. Cytokine concentration of IL-15Ralpha (A), IL-15 (B), TNFalpha (C) and IL-6 (D) were measured in in duplicate SF samples from RA (n = 30) and OA (n = 30) by ELISA. Box plot represents media ± SD. Differences between two groups were performed by Mann–Whitney U test for nonparametric data.
Mentions: Quantification by ELISA of cytokines IL-15Ralpha, IL-15, IL-6, and TNFalpha in synovial fluids from the knee joints of 30 RA and 29 OA patients, showed that SF from RA patients contained significantly higher concentrations of IL-15Ralpha (p = 0.03, Figure 1A), TNFalpha (p = 0.002, Figure 1C) and IL-6 (p = 0.001, Figure 1D) than the OA group, but in the case of IL-15 we did not find any significant difference between RA and OA groups (p = 0.29) (Figure 1B).Figure 1

Bottom Line: We found higher and significant levels of TNFalpha, IL-6 and IL-15Ralpha but not of IL-15 in RA compared with the OA group.In addition we found correlation between the value of IL-15Ralpha in SF and disease activity score, DAS28.Finally, we found a correlation between IL-15Ralpha-IL-6, IL-15Ralpha-IL-15, but we did not find any correlation between other pairs of studied cytokines in SF.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutical Division, Center for Genetic Engineering and Biotechnology, Havana, CP 10600, Cuba. alicia.santos@cigb.edu.cu.

ABSTRACT

Background: Pro-inflammatory cytokines are directly implicated in the pathogenesis of Rheumatoid arthritis (RA). Variable clinical response to cytokine targeted therapies as TNFalpha and IL-6, strongly highlights the heterogeneity of inflammatory process in RA. Another cytokine, IL-15 has also been related to the inflammatory process in RA. Recently we described for the first time, the presence of its specific receptor, IL-15Ralpha, in synovial fluid (SF). The aim of this work was to compare the expression profile of IL-15Ralpha, its ligand IL-15, TNFalpha and IL-6 and how these cytokines are correlated in SF from RA patients taking as a reference Osteoarthritis (OA), an articular but not autoimmune disease.

Methods: Synovial fluids were obtained from the knee joints of 60 patients, 30 with confirmed diagnosis of RA and 30 with OA diagnosis. The levels of TNFalpha, IL-6, IL-15 and IL-15Ralpha were measured by ELISA. A statistical analysis was performed with GraphPad Prism v5.0 using the Mann-Whitney U test and Spearman's rank correlation. A cluster analysis was run in MeV software v4.9.0 and differences across clusters were evaluated by an ANOVA including post-test analysis.

Results: We found higher and significant levels of TNFalpha, IL-6 and IL-15Ralpha but not of IL-15 in RA compared with the OA group. Additionally, a high inter-individual variability in the levels of these 4 cytokines was observed in RA, although we identified 4 patients' subgroups by cluster analysis of cytokines concentration in SF. We also found a positive correlation between IL-15Ralpha-IL-6 and IL-15Ralpha-IL-15, but not for other pairs of cytokines in RA. In addition we found correlation between the value of IL-15Ralpha in SF and disease activity score, DAS28.

Conclusions: In our current work we found a high inter-individual variability in the levels of TNFalpha, IL-6, IL-15 and IL-15Ralpha in SF of RA patients and were identified four principal clusters of cytokines concentration in SF, suggesting the importance of identifying disease subset of patients for personalized treatment. Finally, we found a correlation between IL-15Ralpha-IL-6, IL-15Ralpha-IL-15, but we did not find any correlation between other pairs of studied cytokines in SF.

Show MeSH
Related in: MedlinePlus