Results of twenty years studies on immunity at the preclinical phase of type 1 diabetes mellitus development in children according to the IPDM program: 2. Content of various types of cytokines and chemokines in the blood

Abstract

The aim is to study the content of various types of cytokines and chemokines in the blood of normoglycemic children with burdened heredity which are at the preclinical latent stage of type 1 diabetes mellitus (T1DM) development, that was established on the basis of determining autoantibody titer to the pancreatic islets (OAA) of Langerhans. Methods. To survey 561 normoglycemic children according to the IPDM program, they were divided into four subgroups: 1) 104 — OAA-negative ones without genetic predisposition to T1DM (control); 2) 296 — OAA-negative with a genetic predisposition to T1DM; 3) 161 — OAA-positive to at least two OAA (GADA and IA‑2A) and 4) 86 — those affected with T1DM. Determination of cytokine (IL‑1α, IL‑1β, IL‑4, IL‑6, IL‑10, IFNγ, TNFα) and chemokine (IL‑8 and IL‑16) content in blood serum was performed by ELISA using a reagents set of DIACLONE (France) and DRG (USA) firms. Results. It has been established that a significant increase in the level of proinflammatory cytokines (IL‑1α, IL‑1β, IL‑6 and TNF-α), chemokines (IL‑8 / CXCL8 and IL‑16) and decrease in the level of immunoregulatory cytokines, especially IL‑4 and IL‑10 were observed in the earliest preclinical stage in normoglycemic children positive for at least two islet autoantibodies (GADA and IA‑2A). With the development of disglycemia, the change in the level of cytokines was progressed. When clinically diagnosed T1DM occurs, the elevated titer of OAA and the level of proinflammatory cytokines can be preserved in some patients, indicating that some of them have insulin-producing cells remaining not destroyed despite the onset of the disease and that can serve as a marker for choosing the type of substitution therapy. Conclusion. One of the key mechanisms of the T1DM pathogenesis is the imbalance between proinflammatory and regulatory cytokines.