ABSTRACT
PURPOSE: Little is known regarding the therapeutic effect of carbonic anhydrase inhibitors (CAIs) in the management of cystic macular lesions in children with X-linked juvenile retinoschisis (XLRS) despite the fact that this disease often manifests during childhood. Therefore, our goal was to determine the efficacy of CAIs in the treatment of cystic macular lesions in children with XLRS. METHODS: We used CAIs to treat cystic macular lesions in 18 eyes of nine children with XLRS. We evaluated the therapeutic effect of CAI treatment with the best-corrected visual acuity and foveal zone thickness (FZT) with spectral-domain optical coherence tomography. A reduction of at least 22.4% in FZT was defined as objective evidence of response. RESULTS: Five of nine (55.6%) XLRS patients showed a significant reduction of FZT in both eyes over a median treatment interval of 6.8 months (range, 1-23). In four of five (80.0%) patients, this reduction was already apparent after 1 month of treatment. An improvement of visual acuity was observed in five eyes (27.8%) of three patients (33.3%). Six patients (66.6%) reported minor side effects. CONCLUSIONS: Treatment with CAIs decreased FZT in more than half of the children with XLRS. This effect was observed within 1 month in the majority of patients. Carbonic anhydrase inhibitor treatment restores retinal anatomy and may contribute to creating optimal circumstances for gene therapy.
Subject(s)
Acetazolamide/administration & dosage , Macular Edema/drug therapy , Retina/pathology , Retinoschisis/complications , Visual Acuity , Adolescent , Carbonic Anhydrase Inhibitors/administration & dosage , Child , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Macular Edema/diagnosis , Macular Edema/etiology , Male , Ophthalmic Solutions , Retinoschisis/diagnosis , Retrospective Studies , Time Factors , Tomography, Optical Coherence/methods , Treatment OutcomeABSTRACT
BACKGROUND: The T cell attracting chemokine CCL18 is produced by antigen presenting cells and a role for CCL18 has been suggested in the pathogenesis of a variety of diseases. Rheumatoid arthritis (RA) is one of these conditions, in which abundant CCL18 production is present. Although Th2 cytokines and IL-10 are known to have an effect on CCL18 production, there are several gaps in our knowledge regarding the exact regulation of CCL18 secretion, both in general and in RA. In this study we provide new insights in the regulation of CCL18 secretion by monocytes and dendritic cells. RESULTS: In contrast to a large panel of pro-inflammatory stimuli (IL-1beta, TNF-alpha, IL-10, IL-13, IL-15, IL-17, IL-18, IFN-gamma), T cell mimicking molecules (RANKL, CD40L) or TLR driven maturation, the anti-inflammatory IL-10 strongly stimulated DC to secrete CCL18. On freshly isolated monocytes, CCL18 secretion was induced by IL-4 and IL-13, in strong synergy with IL-10. This synergistic effect could already be observed after only 24 hours, indicating that not only macrophages and dendritic cells, but also monocytes secrete CCL18 under these stimulatory conditions. A high CCL18 expression was detected in RA synovial tissue and incubation of monocytes with synovial fluid from RA patients clearly enhanced the effects of IL-4, IL-13 and IL-10. Surprisingly, the effect of synovial fluid was not driven by IL-10 of IL-13, suggesting the presence of another CCL18 inducing factor in synovial fluid. CONCLUSION: In summary, IL-10 synergistically induces CCL18 secretion in combination with IL-4 of IL-13 on monocytes and monocyte derived cells. The effects of IL-14, IL-13 and IL-10 are strongly enhanced by synovial fluid. This synergy may contribute to the high CCL18 expression in RA.
Subject(s)
Arthritis, Rheumatoid/immunology , Chemokines, CC/biosynthesis , Dendritic Cells/immunology , Interleukins/pharmacology , Monocytes/immunology , Synovial Fluid/immunology , Cells, Cultured , Cytokines/pharmacology , Dendritic Cells/drug effects , Drug Synergism , Humans , Interleukin-10/pharmacology , Interleukin-13/pharmacology , Interleukin-4/pharmacology , Monocytes/drug effects , Toll-Like Receptors/metabolismABSTRACT
In neuro-inflammatory diseases, activated T cells are thought to drive the inflammatory process. In this study, we investigated the potential role of three T cell attracting chemokines (CK) in neuro-inflammation. For this purpose, we measured levels of CXCL16, CCL17 and CCL18 in matched serum and cerebrospinal fluid (CSF) samples of patients with different neurological diseases. Interestingly, CXCL16 levels were significantly elevated in the CSF and were higher in inflammatory disease than in controls, whereas CCL17 and CCL18 were absent in the CSF. CCL18 was only elevated in serum of SLE patients. These data suggest that attraction of activated memory type T cells by CXCL16 might play an important role in the orchestration of immune responses in the central nervous system.
