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Accurate and Simple Measurement of the Pro-inflammatory Cytokine IL-1β using a Whole Blood Stimulation Assay
Published on: March 1, 2011
Time-dependent effects on circulating cytokines in patients with LADA: A decrease in IL1-ra and IL-1 beta is
Ingrid K Hals1, Anneli Björklund2, Hanne Fiskvik Fleiner3
1Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Clinic of Medicine, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Background:
Cytokines and chemokines participate in autoimmune processes at cellular targets which include insulin-producing beta cells. To which extent such participation is reflected in the circulation has not been conclusively resolved.
Aim:
We compared the time course of cytokines/chemokines in Latent Autoimmune Diabetes in Adults (LADA) patients heterogeneous for high or low autoimmune activity as determined by levels of antibodies against glutamic acid decarboxylase (GADA).
Methods:
Serum samples to be measured were from a two-armed randomized controlled trial (RCT) in 68 LADA patients. The study encompassed 21 months with C-peptide as primary endpoint. We measured 27 immune mediators at baseline, at 9 and at 21 months (end of study). Results of measurements were analyzed by multiple linear regression.
Results:
At baseline, a high body mass index (BMI) (>26 kg/m2) was associated with elevated levels of the interleukins (IL) IL-1 beta, IL-1ra, IL-2, IL-5, IL-6 and IL-13. Treatment during RCT (sitagliptin vs. insulin) did not affect the time course (21 months) of levels of cytokines/chemokines (by univariate analyses). However, levels of the cytokines IL-1ra and IL-1 beta decreased significantly (p < 0.04 or less) in patients with high vs. low GADA when adjusted for BMI, age, gender (male/female), treatment (insulin/sitagliptin) and study site (Norwegian/Swedish).
Conclusions:
In LADA, high levels of GADA, a proxy for high autoimmune activity and linked to a decline in C-peptide, was associated with a decrease of selected cytokines over time. This implies that the decline of IL-1ra and IL-1 beta in the circulation reflects autoimmune activity and beta cell demise in LADA.
