Presentation: Il-12 P35 , Il12/23p40 and Il-23 P19 Subunit Expression in Temporal Arterial Lesions from Patients with Giant-Cell Arteritis (GCA) (2007)

128 Il-12 P35 , Il12/23p40 and Il-23 P19 Subunit Expression in Temporal Arterial Lesions from Patients with Giant-Cell Arteritis (GCA)

Background: It is currently believed that GCA lesions develop as a consequence of a Th1-mediated immune response against unknown antigens present in the arterial wall. Interleukin-12 is a heterodimeric cytokine (p35/p40) involved in the Th1 functional differentiation of T lymphocytes. p40 may also form homodimers and, when combining with p19 subunit, conforms IL-23, a powerful pro-inflammatory cytokine. p40 deficient mice are resistant to the induction of experimental chronic inflammatory diseases whereas p35 knock-out mice develop more severe forms, suggesting opposite functions of these subunits in the outcome of chronic inflammatory diseases.
Objectives: To investigate p40, p35, and p19 expression in temporal arteries from patients with GCA.
Methods: P40, p35 and p19 mRNAs were measured by real-time quantitative RT-PCR (Applied Biosystems) in temporal artery biopsies from 29 patients ( 22 women and 7 men) with biopsy-proven GCA and 12 controls. These patients were prospectively evaluated, treated and followed for 3.5 years. Patients were considered to have a weak systemic inflammatory response (SIR) if they had 0-2 of the following at diagnosis: fever (T> 37oC, weight loss ≥ 3 Kg, Hb > 110g/L, ESR ≥ 85mm, and a strong SIR if they had 3-4. Mann-Whitney test was used for statistical analysis.
Results: p40, and p19 mRNA concentrations were significantly higher in patients than in controls (1.68 ± 0.31 relative units vs 0.06± 0.06, p = 0.0004; 29.88± 6.1vs 5.55 ± 1.5, p < 0.0001, respectively). Surprisingly, p35 mRNA levels tended to be lower in patients compared to controls (17.75 ± 2.5 vs 25.67 ± 4.8, p = 0.11). p19 mRNA was significantly more abundant in patients with a strong SIR than in patients with a weak SIR (32.89 ± 3.6 vs 22.8 ± 6.08, p = 0.022).
Conclusions: p40 and p19 mRNA are up-regulated in active lesions from patients with GCA, particularly in those with strong SIR, suggesting that IL23 rather than IL12 may have a pro-inflammatory role in GCA.
Supported by SAF 05/06250 and MTV3 06/0710

 G. Espígol, None.

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