Regulatory Effects of IFN-β on the Development of Experimental Autoimmune Uveoretinitis in B10RIII Mice

BACKGROUND: Experimental autoimmune uveoretinitis (EAU) serves as a model for human intraocular inflammation. IFN-β has been used in the treatment of certain autoimmune diseases. Earlier studies showed that it ameliorated EAU; however, the mechanisms involved in this inhibition are still largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: B10RIII mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) peptide 161-180 in Complete Freund's adjuvant. Splenocytes from different time points after immunization were used to evaluate the expression of IFN-β. An increased expression of IFN-β was observed during EAU and its highest expression was observed on day 16, 3 days after the peak of intraocular inflammation. Splenocytes and draining lymph node cells from mice immunized with IRBP(161-180) on day 13 and control mice were activated with anti-CD3/anti-CD28 antibodies or IRBP(161-180) to evaluate the production of IFN-γ and IL-17. The results showed that IFN-γ and IL-17 were significantly higher in immunized mice as compared to the control mice when exposed to anti-CD3/anti-CD28 antibodies. However, the production of IFN-γ and IL-17 was detected only in immunized mice, but not in the control mice when stimulated with IRBP(161-180). Multiple subcutaneous injections of IFN-β significantly inhibited EAU activity in association with a down-regulated expression of IFN-γ, IL-17 and an enhanced IL-10 production. In an in vitro system using cells from mice, IFN-β suppressed IFN-γ production by CD4(+)CD62L(-) T cells, IL-17 production by CD4(+)CD62L(+/-) T cells and proliferation of CD4(+)CD62L(+/-) T cells. IFN-β inhibited the secretion of IL-6, but promoted the secretion of IL-10 by monocytes. IFN-β-treated monocytes inhibited IL-17 secretion by CD4(+)CD62L(+/-) T cells, but did not influence IFN-γ expression and T cell proliferation. CONCLUSIONS/SIGNIFICANCE: IFN-β may exert its inhibitory effect on EAU by inhibiting Th1, Th17 cells and modulating relevant cytokines. IFN-β may provide a potential treatment for diseases mediated by Th1 and Th17 cells

Traditional Chinese medicines as immunosuppressive agents

Annals of the Academy of Medicine Singapore29111-16AAMS

Improvement in lupus nephritis following treatment with a Chinese herbal preparation

Archives of Pediatrics and Adolescent Medicine1538850-852APAM

The role of skin testing and extended antibiotic courses in assessment of children with penicillin allergy: An Australian experience

Aim To determine if skin testing (ST) in addition to extended oral provocation challenge (OPC) is necessary for beta‐lactam allergy verification in an Australian paediatric population. Methods This was a retrospective study (176 children) that undertook assessments for beta‐lactam allergy from 2006 to 2015 at a tertiary paediatric hospital. Patients either underwent direct OPC without ST or ST plus challenge if ST was negative. Results The analysis included children with a history of varying rash types/severity as well as angioedema and reported anaphylaxis. A direct OPC was undertaken in 73 children. Three children reacted with one anaphylaxis. A total of 103 children underwent ST, with 13 children (12.6%) reacting. Of the 90 who subsequently proceeded to OPC, 4 reacted. A total of 132 children were given an extended oral course of the culprit antibiotic, to which 6 children reacted. Conclusions A direct OPC with the culprit drug in Australian children can be safely performed, avoiding resource‐intensive and painful ST. Our data demonstrate that a prior history of anaphylaxis does not necessarily predict IgE‐mediated allergy, as detected by positive immediate ST or reactions to oral challenge. Such history should not detract from efforts to assess these children for antibiotic allergy. We suggest that extended courses of at least 5 days are important in paediatric antibiotic de‐labelling as six children (4.5% of those who were prescribed the extended course) reacted in our study and even developed symptoms late in the extended course, from days 2 to 6

Geranylated flavonoids from the roots of campylotropis hirtella and their immunosuppressive activities

In an effort to identify new immunosuppressive agents from natural sources, 12 new geranylated flavonoids, 5,7,4′-trihydroxy-3′-[7-hydroxy-3,7- dimethyl-2(E)-octenyl]isoflavone (1), a racemate of 5,7,2′,4′- tetrahydroxy-3′-[7-hydroxy-3,7-dimethyl-2(E)-octenyl]isoflavanone (2), 2″(S)-5,7-dihydroxy[2″-methyl-2″-(4-methyl-3-pentenyl)pyrano] -5″,6″:3′,4′-isoflavone (3), (2″S,3″R, 4″S)-5,7,3″,4″-tetrahydroxy[2″-methyl-2″-(4- methyl-3-pentenyl)pyrano]-5″,6″:3′,4′-isoflavone (4), a racemate of 3′-geranyl5,7,2′,4′-tetrahydroxyisoflavanone (5), a racemate of 3′-geranyl-4′-methoxy-5,7,2′- trihydroxyisoflavanone (6), 3′-geranyl-5,7,4′,5′- tetrahydroxyisoflavone (8), 3′-geranyl-5,7,2′,5′- tetrahydroxyisoflavone (9), 3′-geranyl-4′-methoxy-5,7,2′- trihydroxyisoflavone (10), 2(R),3(R)-3′-geranyl-2,3-trans-5,7,4′- trihydroxyflavonol (12), (2R,3R)-6-methyl-3′-geranyl-2,3-trans-5,7, 4′-trihydroxyflavonol (13), and 5,7-dihydroxy4′-O-geranylisoflavone (14), were isolated from the roots of Campylotropis hirtella (Franch.) Schindl. together with three previously described flavonoids. Their structures were elucidated by spectroscopic measurements, including two-dimensional nuclear magnetic resonance (NMR) techniques. The immunosuppressive effects of these compounds were assessed using mitogen-induced splenocyte proliferation, and the cytotoxicity of the compounds was also examined. The IC50 values of the compounds were found to be in the range of 1.49-61.23 μM for T lymphocyte suppression and 1.16-73.07 μM for B lymphocyte suppression. An analysis of their structure-activity relationships revealed that an isoflavonoid carbon skeleton with a C10 substituent at the C3′ position was necessary for the activity. As many of the compounds exhibited good immunosuppressive activities, they may be promising as novel immunosuppressive agents