SUMMARYAs Q fever is associated with an in¯ammatory syndrome, we determined circulating levels of in¯ammatory cytokines, cytokine antagonists, and activation markers of leucocytes in patients with acute Q fever and Q fever endocarditis. Tumour necrosis factor (TNF) and IL-6, but not IL-1b, were markedly increased compared with controls. Cytokine antagonists and activation markers of leucocytes were profoundly different in acute and chronic Q fever. IL-1 receptor antagonist and TNF receptor type II were signi®cantly increased in patients with acute Q fever, suggesting a shift of cytokine balance towards cytokine antagonists. The activation marker of B cells, sCD23, was signi®cantly increased in Q fever endocarditis compared with controls and patients with acute Q fever. In a 2-year follow-up study of patients with Q fever endocarditis, sCD23 and speci®c IgG levels slowly decreased in patients whose symptoms resolved, but remained high in those who required prolonged treatment.
SUMMARYQ fever is an infectious disease caused by Coxiella burnetii, an obligate intracellular microorganism that inhabits monocytes/macrophages. The dysregulated production of TNF-a in Q fever endocarditis has been associated with defective killing of C. burnetii by patient monocytes. As soluble receptors for TNF-a (TNF-R55 and TNF-R75) regulate TNF-a activity, we investigated their release by monocytes in Q fever. Spontaneous and C. burnetii-stimulated release of TNF-R75, but not of TNF-R55, was upregulated in patients with ongoing endocarditis compared with controls. The increase in TNF-R75 release was related to the activity of Q fever endocarditis, since TNF-R75 release was similar in patients with cured endocarditis and controls. While spontaneous release of TNF-R75 by monocytes from patients with ongoing Q fever endocarditis occurred without changes in its membrane expression, C. burnetii increased the surface expression of TNF-R75. In addition, TNF-R75 transcripts were increased in resting and C. burnetii-stimulated monocytes from patients with ongoing endocarditis. On the other hand, TNF-R75 release was not related to TNF-a secretion. These results indicate that the modulation of TNF-R75 is a critical feature of the pathophysiology of Q fever endocarditis.
Murine T and B splenocytes were incubated with antibodies that recognize CD3 or surface IgM. These antibodies induced proliferation of their respective target cells. Once stimulated via their receptors, the proliferation of both CD4+ and CD8+ T but not B lymphocytes was inhibited by class I-specific antibodies or their monovalent Fab' fragments. The inhibition of proliferation was dependent on the site on class I molecules recognized by the antibodies used, with the alpha 1/alpha 2 domains of H-2K molecules representing the major site for inhibition. Only soluble antibody-mediated proliferation could be inhibited by class I-directed antibodies; proliferation induced by CD3-specific antibody immobilized on plastic was not inhibited. Primary allogeneic MLR was also inhibited by class I-specific antibodies. In contrast, neither secondary allogeneic MLR, secondary Ag-specific responses, nor proliferation of CTL clones or tumor cell lines were inhibited by class I-specific antibodies. These results suggest a role for class I molecules in regulation of TCR/CD3- but not surface IgM-mediated cell signaling, which depends on the form of stimulation and the stage of differentiation of T cells.
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