Disturbed Cytokine Profile in Adjuvant Arthritis – A Target of the Therapeutic Potential of Dendritic Cells Derived From Cryopreserved Precursors

Abstract

Background. One of the primary causes of rheumatoid arthritis development is the disruption of the immune system's natural tolerance to its own antigens, leading to an imbalance in the body's cytokine profile. A promising method of correcting such a condition is restoring antigen-specific tolerance, in the formation of which tolerogenic dendritic cells (tolDCs) take part. Objective. Experimental substantiation of the possibility of correcting the cytokine profile of animals with adjuvant arthritis (AA) by using tolDCs from cryopreserved bone marrow precursors. Methods. The study was carried out on the CBA/H mice. The development of AA was assessed using a clinical indicator – the arthritis index. The levels of pro- (TNF-a, IL-6, IFN-g) and anti-inflammatory (IL-10, IL-4) cytokines in the blood serum of AA-afflicted animals were measured before and after administration of tolDCs. These tolDCs were obtained from native (NatDCs) or cryopreserved (CryoDCs) using different methods bone marrow mononuclear cells (MNCs). On the 14th day after inducing AA, the animals received intravenous injections of tolDCs (5´105/mouse). One week later, the cytokine levels in the animals' blood serum and the arthritis index were assessed. Results. Throughout the development of AA, a unidirectional increase in TNF-α and IL-6 levels and a reduction in the content of anti-inflammatory cytokines were observed, which was accompanied by joint swelling in the animals. CryoDCs exhibited a more pronounced corrective effect on both pro- and anti-inflammatory cytokines compared to NatDCs, as evidenced by a decrease in the arthritis index, a clinical manifestation of the pathology. Conclusions. The possibility of correcting the disturbed cytokine profile and the clinical state of animals during the development of AA through the use of tolDCs derived from cryopreserved MNCs has been proven. Specific cryopreservation conditions for MNCs have been developed, which facilitate the generation of tolDCs from them with a greater capacity, compared to derivatives of native MNCs, to correct the cytokine profile and clinical status of animals with AA.