Hormonal dysfunction involving the hypothalamic-pituitary-adrenal (HPA) axis, prolactin (PRL) secretion and sex hormone status has been supposed to contribute to the development or persistence of rheumatoid arthritis (RA). In addition, a reduced number of glucocorticoid receptors on circulating lymphocytes has been found in patients with RA. However, so far most studies have been performed in pre-treated patients. A combined test for total anterior pituitary reserve was performed in 10 patients with newly diagnosed untreated RA. Before and after stimulation with the respective hypothalamic releasing hormones, RA patients showed no difference in plasma concentrations of adrenocorticotrophic hormone (ACTH), cortisol, prolactin (PRL) and thyroid-stimulating hormone (TSH) when compared to healthy controls. In contrast, the growth hormone (GH) response to growth hormone-releasing hormone (GHRH) was blunted in RA patients. The hypothalamic-pituitary-thyroid/gonadal and adrenal axes seem to be unaltered in RA. However, if one considers the presence of chronic inflammation, normal plasma ACTH and cortisol concentrations must be considered as inappropriately low. The observed blunted GH release could be mediated by cytokines (e.g. IL-1), which are known to be elevated in RA.
Spontaneous growth of myeloid colonies (colony-forming unit–granulocyte-macrophage [CFU-GM]) can be observed in methylcellulose cultures containing peripheral blood mononuclear cells (PB-MNCs) and is supposedly caused by the release of colony-stimulating factors (CSF ) by accessory cells. Because of its cytokine synthesis-inhibiting effects on T lymphocytes and monocytes, interleukin-10 (IL-10) may be a potential candidate for indirect modulation of hematopoiesis. We studied the effect of recombinant human IL-10 (rhIL-10) on spontaneous growth of myeloid colonies derived from human PB-MNCs. A total of 10 ng/mL of IL-10 almost completely inhibited spontaneous CFU-GM proliferation (by 95.1%; P < .001, n = 7) in unseparated PB-MNCs. This effect was dose-dependent and specific, because a neutralizing anti–IL-10 antibody was able to prevent IL-10–induced suppression of CFU-GM growth. Spontaneous CFU-GM growth, which required the presence of both monocytes (CD14+ cells) and T lymphocytes (CD3+ cells), was also greatly suppressed by a neutralizing anti–granulocyte-macrophage CSF (GM-CSF ) antibody but was only slightly or not at all inhibited by antibodies against G-CSF or IL-3. Moreover, IL-10–suppressed colony growth could be completely restored by the addition of exogenous GM-CSF. Using semiquantitative polymerase chain reaction, we were able to show that GM-CSF transcripts that spontaneously increased in PB-MNCs within 48 hours of culture were markedly reduced by the addition of IL-10. Inhibiton of GM-CSF production in PB-MNCs by IL-10 was also confirmed at the protein level by measuring GM-CSF levels in suspension cultures. Our findings suggest that autonomous CFU-GM growth, resulting from an interaction of monocytes and T lymphocytes, is mainly caused by endogenous GM-CSF release and can be profoundly suppressed by the addition of exogenous IL-10. Considering the strong inhibitory action of IL-10 on GM-CSF production and spontaneous cell growth in vitro, this cytokine may be useful in myeloid malignancies in which autocrine and/or paracrine mechanisms involving GM-CSF are likely to play a pathogenetic role.
Recurrent arthritis, fever and lymphadenopathy are symptoms of adult onset of Still's disease (AOSD). Differential diagnosis requires the exclusion of infections or malignant lymphomas. We report on a case of AOSD showing destructive lymphadenopathy, immunophenotyping of peripheral blood leucocytes revealed strong activation of T-lymphocytes. Bone marrow biopsy also showed an increase of lymphopoietic cells to 23%. Analysis of peripheral blood lymphocytes (PBL) after remission showed no remaining signs of activation. Analysis of lymphocyte activation by flow cytometry correlated with disease activity.
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