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.

• Authors: Nikola Smatlik, Nourhan Mortada, Martin Röcken, Amir S Yazdi, Manfred Zierhut
• Journal: Ocular immunology and inflammation (Ocul Immunol Inflamm) Vol. 30 Issue 6 Pg. 1369-1377 (Aug 2022) ISSN: 1744-5078 [Electronic] England
• PMID: 33793375 (Publication Type: Journal Article)

Chemical References

• HLA-B27 Antigen
• Mesalamine
• Cytokines

Topics

• Humans
• HLA-B27 Antigen (genetics)
• Mesalamine (pharmacology, therapeutic use)
• Cytokines (genetics)
• Uveitis, Anterior (drug therapy, genetics)
• Acute Disease