Mesalazine Suppresses Proinflammatory Cytokines in Patients with Acute Anterior Uveitis Independently of HLA-B27

ABSTRACT

Purpose

The aim is to unravel the mechanism of mesalazine (5-ASA) on proinflammatory cytokines in PBMCs of patients with HLA-B27 +and HLA-B27 -acute anterior uveitis (AAU), and whether this may explain the different effects of 5-ASA in both disoders.

Methods

PBMCs from 12 HLA-B27+ and 4 HLA-B27- AAU patients were preincubated with 5-ASA and stimulated with LPS. As mesalazine (5-ASA) could be involved in ER stress, proinflammatory and ER stress-associated cytokines and markers were measured.

Results

Mesalazine (5-ASA) suppressed IL-6 mRNA in healthy donors and in HLA-B27+ and HLA-B27- patients but did not lead to induction and secretion of IL-1β. In HLA-B27 + or – patients the ER stress-associated markers CHOP (DDIT3) and ATF6 were suppressed.

Conclusions

Here we show that mesalazine (5-ASA) inhibits the transcription of proinflammatory and (ER) stress associated cytokines and markers, independently of the HLA-B27 status. Results show the similarities of both AAU types but do not decipher the mechanism why the HLA-B27 status determines the therapeutic response to mesalazine in AAU.

KEYWORDS:

• Uveitis
• mesalazine
• ER stress
• HLA-B27
• inflammation
• cytokines

Acknowledgments

We want to thank the Deutsche Forschungsgemeinschaft (DFG) Sonderforschungsbereich (SFB) transregio (TRR)156, project B06 (to MR and ASY) for financial support of this work.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This work was supported by the Deutsche Forschungsgemeinschaft [Sonderforschungsbereich (SFB) transregio (TRR)156].