Secondly, parallel usage of subcutaneous and peroral immunisations shows that SASP affects both systemic and gut\associated immunity, observed as changes in IgA\SFC and IgG\SFC in peripheral blood after immunisations. at 6, 8 and 10?days after immunisation. Results An immunosuppressive effect of SASP on systemic immune response was observed with a decrease in the total number of IgG\SFC, IgG anti\tetanus SFC and IgG anti\tetanus antibody levels in serum. SASP also exerted an immunosuppressive effect on the mucosa\associated immune system as seen from its down\regulating effect on the total number of circulating IgA SFC. Conclusions These data show firstly that SASP exerts an immunosuppressive effect on defined immune responses to immunisation in vivo, and secondly that both mucosa\associated and systemic immunity are affected by SASP treatment. Development of therapeutic strategies against inflammatory diseases such as rheumatoid arthritis today make use of several different Poziotinib options, among them combination therapies with new as well as older drugs. A rational use of these therapies requires more knowledge on the mode of action of all the drugs used, and also on their potential adverse effects, such as a reduced immune defence against various microbes. In many cases, however, even the effects of well\accepted and commonly used antirheumatic drugs on immune responses are unknown. This is at least partly due to the lack of adequate methods to describe the effects of antirheumatic drugs on adaptive immune responses in vivo in humans. In this study, we wanted to investigate whether a vaccination protocol followed by evaluation of the adaptive immune response by means of analysis of immunoglobulin\producing Poziotinib cells could be used as a tool to study the effects of an antirheumatic drug on adaptive immune responses. Specifically, the effects of sulphasalazine (SASP) on host adaptive immune responses to Poziotinib the antiviral influenza vaccine and to the antibacterial tetanus toxoid vaccine were investigated. SASP has been marketed for many years and is still commonly used both as monotherapy against arthritis and inflammatory bowel disease, and as a component in various combination therapies for rheumatoid arthritis.1,2,3,4,5 Nevertheless, surprisingly little is known about the effects of SASP on an immune response in vivo. We know that the treatment of patients with rheumatoid arthritis and additional inflammatory diseases in vivo causes reduction of inflammatory guidelines such Poziotinib as sedimentation rate and acute\phase reactants, and may lead to a decrease in serum immunoglobulin levels.6,7,8,9,10 In vitro experiments have documented effects both on non\specific inflammatory events such as granulocyte and mast cell activation, and on lymphocyte functionsthat is, SASP can, in certain concentrations, inhibit both T and B cell proliferation, and immunoglobulin production.8,11,12,13,14,15,16 In addition, the inhibition of macrophage activation and NfkB\dependent transcription has been described.17,18 The fact the in vitro effects on lymphocyte function are seen for concentrations of SASP, which in vivo are only encountered within the gut, offers supported the hypothesis that SASP preferentially exerts its action within the gut\associated immune system.19,20,21 However, we still, we do not know to what degree SASP in vivo affects the adaptive immune response triggered from your gut or systemically. One of the hurdles in studying immune responses induced in the gut resides in the fact that mucosa\derived immunity is only incompletely reflected by changes in the serum levels of IgA; instead, bone marrow cells are Mouse monoclonal to CD95(PE) the main source of IgA in serum. A potential way to overcome this problem has been highlighted by data indicating that IgA production of B lymphocytes in the blood displays a mucosa\connected immune response much better than serum IgA levels.22,23,24 To study the mode and the site of action of SASP on defined immune response in vivo, we immunised healthy individuals inside a increase\blind manner perorally and systemically after treatment with SASP or placebo for 2?weeks. Immune responses were evaluated by measuring both circulating Ig\generating cells of different isotypes with the enzyme\linked immunospot (ELISPOT) assay and serum immunoglobulin levels. In this way, we were able to evaluate the effects of SASP on both the systemic and the mucosa\connected immune responses. Methods Study subjects A total of 25 healthy volunteers, aged 17C48 (imply 32)?years were recruited mainly.
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