Objective. To investigate the presence and role of interleukin-17 (IL-17) in rheumatoid arthritis (RA), and its regulation by antiinflammatory cytokines.Methods. The production of IL-17 was measured in supernatants of RA, osteoarthritis (OA), and normal synovial tissue pieces cultured ex vivo. Quantification of IL-17 was performed using a specific biologic assay. IL-17 gene expression was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR)-techniques. Immunohistochemistry was used to evaluate the frequency of IL-17-positive cells in synovium.The secretion of IL-17 by synovium was measured in the presence of IL-4, IL-13, and IL-10. In addition, the contributions of exogenous and endogenous IL-17 to IL-6 production by RA synovium were studied.Results. Functional IL-17 was spontaneously produced by 16 of 18 RA (mean ؎ SEM 41.7 ؎ 11.4 units/ml), 2 of 12 OA (5.3 ؎ 4.5 units/ml), and 0 of 3 normal synovial explant cultures. IL-17 messenger RNA expression was demonstrated by RT-PCR in 4 of 5 RA and 0 of 3 OA synovial samples. By immunostaining of RA synovium, IL-17-producing cells were found in the T cell-rich area. Addition of both IL-4 and IL-13 completely inhibited the production of IL-17, whereas IL-10 had no effect. Addition of exogenous IL-17 to RA synovium resulted in an increase in IL-6 production, whereas that of a blocking anti-IL-17 antibody reduced production of IL-6.Conclusion. The T cell cytokine IL-17 was found to be highly produced by RA, but not by OA, synovium. Its production and function were down-regulated by IL-4 and IL-13. These results indicate that IL-17 contributes to the active, proinflammatory pattern that is characteristic of RA. Through the contribution of IL-17, some Th1-like T cells appear to mediate synovial inflammation.

isrctn.org Identifier: ISRCTN54371254.

Mediterranean spotted fever due to infection by Rickettsia conorii, is characterized by a general vasculitis. This vasculitis is thought to be due to a direct injury to endothelial cells induced by R. conoryi However, production and activity of cytokines on endothelial cells is an important pathway in inflammation, and part of the underlying mechanism of vasculitis. In the present studies, human umbilical vein endothelial cells (HUVEC) infected with R. conorii actively secrete high levels of IL-8 and IL-6 (P < 0.002, and P < 0.03, respectively, compared with uninfected cells). IL-la, IL1j3, or TNFa were not detected in the culture supernates.Nevertheless, IL-6 and IL-8 production was due, in a large part, to a cell-associated form of IL-la expressed on R. conorii-infected HUVEC, since production of these cytokines was suppressed by 80% (P = 0.0001) and 85% (P < 0.04) by the addition of IL-1 receptor antagonist, or anti-IL-la antibodies (60% inhibition, P < 0.01 and 65% inhibition, P < 0.05, respectively) and IL-la was measured after lysis of R. conorii-infected HUVEC but not in uninfected cells (P < 0.01). Rickettsial lipopolysaccharide does not seem to be involved, since polymyxin B did not reduce cytokine secretion. On the contrary, infection by intracellular R. conorii appears to be necessary to induce IL-la and subsequently IL-8, since formalin-fixed R. conorii did not induce cytokine production. These observations demonstrate that R. conorii-infected HUVEC secrete IL-6 and IL-8 via the induction of cell-associated IL-la, providing a possible mechanism for the vasculitis observed in Mediterranean spotted fever. (J. Clin. Invest. 1995Invest. . 96:2839Invest. -2844

A 53-year-old man presented with acute loss of vision, negative scotoma and dyschromatopsia in his left eye. He reported contact with people with severe respiratory syndrome -coronavirus-2 (SARS-CoV-2) 8 days prior symptoms. Funduscopic examination revealed several retinal hemorrhages. Spectral-domain optical coherence tomography showed lesions consistent with acute macular neuroretinopathy and paracentral acute middle maculopathy. Quickly after his presentation, SARSCov-2 was confirmed by chest computed tomography-scan and RT-PCR in this patient. Thrombotic complications associated with Covid-19 infection have high incidence and may involve the retina. We described a case of retinal involvement associated with Covid-19 infection. Précis: Funduscopic examination revealed retinal hemorrhages in a man with loss of vision. Optical coherence tomography showed an acute macular neuroretinopathy and paracentral acute middle maculopathy. Coronavirus disease was confirmed by chest computed tomography-scan and RT-PCR.

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IV. Retrospective therapeutic study.

Enzyme linked immunoassay for the detection of platelet associated IgG: Br J Haematol 48:39, 1981. Cines DB, Schreiber AD: Immune thrombocytopenia: Use of a Coomb's antiglobulin test to detect IgG and C3 on platelets: N Engl J Med 300:106, 1979. Sugiura K, Steiner M, Baldini MG, Pawtnckect RE: Platelet antibody in idiopathic thrombocytopenic purpura and other thrombocytopenias. A quantitative sensitive and rapid assay: J Lab Clin Med 96640, 1980. Von dem Borne AEG KR, Verheugt FWA, Oosterhof F, von Riesz E, de la Rivere .4B, Engelfriet C P A simple immunofluorescence test for the detection of platelet antibodies: Br J Haematol 39:195, 1978.