Serum cytokine profiles in relapsing polychondritis suggest monocyte/macrophage activation

Objective There is evidence that autoimmunity plays a significant role in the pathogenesis of relapsing polychondritis (RP). This study was designed to investigate circulating levels of various cytokines in relation to the etiology of this rare disorder, and to compare the pattern of cytokine elevations in RP with that in another autoimmune disease, rheumatoid arthritis (RA). Methods Serum from 22 patients with active RP and an equal number of age- and sex-matched healthy controls and RA patients were available for analysis. The following cytokines were measured: interleukin-1β (IL-1β), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, interferon-γ (IFNγ), tumor necrosis factor α, granulocyte colony-stimulating factor (G-CSF), granulocyte–macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1β (MIP-1β). Results were analyzed by nonparametric Mann-Whitney test with Holm stepdown adjustment for multiple testing. Results The levels of 3 of these cytokines showed significant differences between RP patients and controls. Compared with controls, mean serum levels of MCP-1, MIP-1β, and IL-8 were all much higher in patients with active RP. In contrast, RA patients showed a more general increase in all cytokines measured, with much higher levels of IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-13, IFNγ, G-CSF, GM-CSF, MCP-1, and MIP-1β compared with controls. Conclusion Levels of 3 serum cytokines were significantly higher in RP patients than in age- and sex-matched controls. One of these 3 cytokines, IL-8, was not significantly elevated in RA samples. Overall, in RP, a more discrete group of cytokines exhibited significantly increased levels than was found in RA. Each of the 3 cytokines that were elevated in RP is a proinflammatory chemokine, characteristic of activation of the monocyte and macrophage lineage, and in the case of IL-8, also of neutrophils. These data suggest a major role for a cell-mediated immune response in the pathophysiology of RP.