ABSTRACT
BACKGROUND: We investigated the effect of chitin on the inflammation and immune modulation of the nasal mucosa. This compound was compared to placebo and as a positive control we used lipopolysaccharide (LPS). METHODS: Fourteen healthy nonsmoking volunteers 22 to 28 years of age were included. All persons underwent exposure to chitin microparticles (CP) and placebo in a randomized double-blinded fashion. In a last session we used LPS from Enterobacter agglomerans in a single-blinded fashion. There were 2 weeks between each session. The outcome measures were Total Nasal Symptom Score (TNSS) and nasal lavage for cytokines and cells at 0, 3, 4, 8 hours. RESULTS: We showed that CP was only weakly inflammatory compared to LPS. In contrast to the LPS response, we did however show an immune-regulatory effect of CP on enhanced interleukin (IL)-4 and IL-6 responses known to downregulate T helper 2 (Th2) responses, indicating a potential beneficial effect of CP for the regulation of the allergic Th2 immune response. CONCLUSION: This study also shows that CP is well tolerated in healthy volunteers, and that does not induce significantly more symptoms compared to placebo. In fact there is a tendency for CP instillation to induce less rhinorrhoea compared to placebo.
Subject(s)
Chitin/pharmacology , Lipopolysaccharides/pharmacology , Nasal Mucosa/metabolism , Rhinitis/metabolism , Administration, Intranasal , Adult , Biomarkers/metabolism , Cell Count , Chitin/administration & dosage , Cross-Over Studies , Cytokines/metabolism , Double-Blind Method , Down-Regulation , Female , Healthy Volunteers , Humans , Immunity, Humoral/physiology , Interleukin-4/metabolism , Interleukin-6/metabolism , Lipopolysaccharides/administration & dosage , Male , Nasal Mucosa/immunology , Nasal Obstruction/chemically induced , Pruritus/chemically induced , Rhinitis/immunology , Single-Blind Method , Sneezing/drug effects , Th2 Cells/immunology , Young AdultABSTRACT
Despite the recent introduction of several new biological products, there remains a significant unmet medical need in rheumatoid arthritis. A focus on the aberrant activation of autoimmune T cells, which is integral to pathogenesis, is a promising approach involved in several of these new therapies. In choosing a molecular target for the modification of T-cell function, it is argued in this article, that within co-stimulatory pathways, CD80 could have a more compelling rationale than CD86. Data are presented showing that CD80-mediated T-cell activation can be inhibited using a small-molecule antagonist, which offers the potential to prevent the inflammatory process leading to joint destruction.
