Background/Purpose: In rheumatoid arthritis (RA) and collagen-induced arthritis (CIA) the phenomenon of a relative insufficiency of adrenal glands to produce an adequate amount of anti-inflammatory glucocorticoids in later stages of the disease is well known (Spiess et al 2014, Wolff et al. 2015). At the same time, the presence and migration of macrophages and dendritic cells (DCs) in and into endocrine organs like the pituitary gland and the adrenal glands has been described (Glennon et al. 2015, Sato 1998, Engstrom et al. 2008). We hypothesized that resident and/or invading immune cells like DCs contribute to the inadequate secretion of endogenous glucocorticoids from adrenocortical cells during arthritis. The aim of this study is to elucidate first possible paracrine mechanisms between local DCs and adrenocortical cells and secondly to manipulate these pathways in order to prevent relative adrenocortical insufficiency in arthritis.

Methods: Cells from whole adrenal glands were harvested and cultured while DCs were differentiated from bone marrow, which was collected from healthy control and arthritic DA rats. Cytokine levels in supernatants from DCs and adrenal gland cells were analyzed by proteome profiler and ELISA. Corticosterone response upon stimulation with ACTH in a co-culture system of adrenal gland cells from control rats and DCs generated from control or arthritic rats was quantified with ELISA.

Results: Analysis of cytokine protein expression revealed a similar profile of the C-X-C ligand chemokines CINC-1, -2, -3 (Cytokine-induced neutrophil chemoattractant), LIX (LPS-induced CXC chemokine) and of the cytokine IL-1β in supernatants from DCs and adrenal gland cells. DCs generated from rats with CIA expressed significantly higher amounts of IL-1β, CINC-1, -2, -3, and LIX (all p<0.001) compared to DCs from control animals. Expression of IL-1β (p<0.001) and CINC-2 (p=0.034) in supernatants from arthritic adrenal gland cells was significantly higher than in supernatants from control cells. Co-culture experiments revealed an inhibitory effect of DCs from control and CIA rats on the corticosterone response of adrenal gland cells upon stimulation with ATCH.

Conclusion: DCs are present in the adrenal gland and seem to inhibit corticosterone production physiologically and during arthritis, possibly via expression of IL-1β and the CXC chemokines CINC-1,2,3 and LIX. Specific targeting of these cells and these chemokines might prevent progression of arthritis by inhibiting the relative adrenal gland insufficiency and, hence, could be a future therapy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/intraadrenal-dendritic-cells-inhibit-corticosterone-response-during-collagen-induced-arthritis-a-role-for-il-1%ce%b2-and-cxc-chemokines/