AGE AND LOW LEVELS OF CIRCULATING VITAMIN D ARE ASSOCIATED WITH IMPAIRED INNATE IMMUNE FUNCTION AND CIRCULATING CYTOKINE DISREGULATION

L. Alvarez-Rodriguez, M. Lopez-Hoyos, M.T. Garcia-Unzueta, J.A. Amado, V.M. Martinez-TaboadaRheumatology Immunology Endocrinology, Hospital Universitario Marques de Valdecilla, Santander, SpainObjectives: To investigate in vivo the influence of vitamin D status and age on innate immune function and circulating cytokine production in healthy subjects. Methods: Serum 25-hidroxy-vitamin D (25-(OH)-D) and PTH levels were measured in 71 healthy subjects. Circulating cytokines were measured by CBA. Intracellular cytokines were assessed in CD3+ and CD14+ cells by flow cytometry. TLR expression on various subpopulations of PBMCs as well as TLR function by stimulating PBMCs with specific ligands were assessed by flow cytometry. Results: Serum 25-(OH)-D levels decreased with age, Pearson coefficient correlation (r=-0.399; p=0.001). Expression of TLR7 on B cells (r=-0.39; p=0.02), T cells (r=-0.35; p=0.05) and monocytes (r=-0.43; p=0.01) measured as mean fluorescence intensity (MFI) was negatively correlated with serum 25-(OH)-D levels. Interestingly enough, TLR7 function addressed by in vitro stimulation with the specific agonist imiquimod was significantly correlated with serum 25-(OH)-D levels, and this was especially due to the results in healthy subjects older than 60 years. MFI expression of TLR5 on T cells (r=-0.34; p=0.04) and TLR8 on monocytes (r=-0.37; p=0.04) were also negatively correlated with serum 25-(OH)-D levels. TLR1 expression on T cells (r=0.32; p=0.04) and monocytes (r=0.40; p=0.01) was correlated with age. Furthermore, TLR2, TLR4, TLR5, TLR6 and 8 function addressed by in vitro stimulation with a specific agonists were negatively correlated with age. Serum 25-(OH)-D levels were negatively correlated with the circulating levels of pro-inflammatory cytokines (TNF-a and IL-6) and the anti-inflammatory cytokine IL-10. Age was positively correlated with the circulating levels of pro-inflammatory cytokines (TNF-a, IL-1b and IL-6), the anti-inflammatory cytokine IL-10 and a Th1 cytokine IL-12. Conclusion: Serum 25-(OH)-D levels decrease with age and are accompanied by a change in expression and defective function of certain TLRs, especially those involved in viral response. Age and vitamin D also have a clear impact in the production of circulating cytokines. The present work is supported by grants from: MSC-Instituto de Salud Carlos III (PI050475/PI080098) and IFIMAV. Disclosure of Interest: None declaredCitation: Annals of the Rheumatic Diseases, volume 69, supplement 3, year 2010, page 167Session: Cytokines and inflammatory mediators (Poster Presentations )