Cytokine profile of the rheumatoid nodule suggests that it is a Th1 granuloma

Abstract

Objective. To define the cytokine profile within rheumatoid subcutaneous nodules, and to determine whether the destructive inflammatory process in this lesion displays features of a lymphocyte-driven Th1 or Th2 granuloma.Methods. Subcutaneous nodules excised from 10 patients with rheumatoid arthritis were examined. Conclusion. The cytokine profile within the rheumatoid nodule (i.e., presence of IFN␥ but not IL-2, and prominent expression of IL-1␤ and TNF␣ together with IL-12, IL-18, IL-15, and IL-10) is similar to the profile of cytokines in the synovial lesion of rheumatoid arthritis, which is generally accepted as being attributable to a Th1-mediated inflammatory mechanism. Our results suggest that damage to affected synovial membrane or subcutaneous tissue is caused by the same inflammatory mechanisms, and that the nodule is a Th1 granuloma.

Proinflammatory mediators elicit secretion of the intracellular B-lymphocyte stimulator pool (BLyS) that is stored in activated neutrophils: implications for inflammatory diseases

“…Neutrophils, in fact, not only produce and release BLyS more rapidly than monocytes or monocyte-derived dendritic cells, 5,6 but, according to the findings presented in this study, they could represent ideal target cells for G-CSF or IFN-␥ acting in combination with CXCL1, CXCL8, TNF-␣, immune complexes, C5a, and LTB 4 , which are all present at high levels in inflammatory synovial fluids. 10,39,40 Therefore, neutralization of the capacity of neutrophils to release soluble BLyS might offer a novel target to halt the activation of B cells and, consequently, interfere with the maintenance of an inflammatory state in several chronic inflammatory diseases.…”

Tocilizumab and Regression of Rheumatoid Nodules in Patients with Rheumatoid Arthritis: 2 Case Reports

“…For instance IL-6 and IL-23 expression was identified in the majority of the analyzed nodules in one study [18] whereas in another work, the profile was different as the RNs commonly expressed TNFα (i.e., presence of IFNγ but not IL-2, and prominent expression of IL-1β and TNF together with IL-12, IL-18, IL-15, and IL-10) [1]. Taking the latter results into consideration, the TNFα blockade should hypothetically at least be able to abolish these TNF dependent nodules.…”

“…They are usually associated with severe form of RA and RF seropositive patients. Histologically, RNs are type-1-driven granulomata [1] and characterized by triple layered rheumatoid granuloma with central core of fibrinoid necrosis, a middle layer of palisading fibroblasts and histiocytes, and outer layer of granulation tissue [2,3]. RNs usually cause little in the way of problem however; in some cases they may become painful especially if the overlying skin breaks down.…”

Exaggerated circulating Th-1 cytokine response in early rheumatoid arthritis patients with nodules

“…Histopathologically, the RN is an immune granuloma consisting of a central area of necrosis, surrounded by a palisade of macrophages and fibroblasts, and a peripheral vascular area containing T lymphocytes and macrophages. A number of studies have drawn comparisons between RN and rheumatoid synovium, describing similarities between the tissues with respect to cellular components, immunohistochemical features and cytokine production (3,4).…”