Anakinra (Kineret), a recombinant form of human interleukin-1 (IL-1) receptor antagonist, is approved for the treatment of rheumatoid arthritis (RA) in combination with methotrexate. Kineret is self-administered by daily subcutaneous injections in patients with active RA. The mechanism of action of anakinra is to competitively inhibit the local inflammatory effects of IL-1. Kineret is generally safe and well tolerated and the only major treatment-related side effects that appear are skin reactions at the injection site. Due to the relatively short half-life of anakinra, daily injection of the drug is required. This, in combination with the comparably high rates of injection-site reactions (ISRs) associated with the drug, can become a problem for the patient. The present review summarises published data concerning ISRs associated with Kineret and provides some explanations as to their cause. The objective is also to present some clinical experiences of how the ISRs can be managed.
SUMMARYMajor histocompatability complex (MHC ) class II genes are important in the pathogenesis of insulin-dependent diabetes mellitus ( IDDM ) both in the mouse and in man. The non-obese diabetic ( NOD) mouse, which is a good model for human IDDM, has a particular MHC class II with an A complex consisting of Aad and the unique Abg7 chain, as well as an absent E molecule due to a deletion in the Ea promoter region. Transgenic insertion of a functional Ea gene protects against insulitis and diabetes, but when the transgene expression is restricted to certain compartments of the immune system by deleting parts of the promoter region, the protection against insulitis is disrupted. We have analysed three promoter-mutated lines where one lacks expression on B cells and has a reduced expression on approximately 1/3 of the dendritic cells and macrophages (Sma), one lacks thymic cortical expression and has a slightly reduced B-cell expression (DX ), and one lacks expression in the thymic medulla, on macrophages, dendritic cells and about half of the B cells (DY ). None of these lines is protected against insulitis, but Sma and DX display a reduced intensity of insulitis, with an average of 10-15% of the islets infiltrated in each mouse, while DY resembles non-transgenic mice with 30-35% infiltrated islets. Bone-marrow chimeras between Sma and DY mice demonstrate that peripheral cells of Sma origin reduce insulitis significantly when developed in the DY host, while insulitis is enhanced when DY bone marrow is given to Sma mice. This shows that E expression on the primary antigen-presenting macrophages and dendritic cells is of crucial importance to the alleviation of insulitis.
INTRODUCTIONdenoted Abg7.3 Several studies have demonstrated the possibility of protecting NOD mice from insulitis and diabetes by Insulin-dependent diabetes mellitus ( IDDM ) is an autotransgenic insertion of a functional Ea gene or the genes for immune disease caused by destruction of the insulin-producing a normal A complex.4-8 When the expression of the Ea gene b cells in the pancreatic Langerhans' islets. The destruction of is restricted to certain compartments of the immune system the b cells is preceded by a mononuclear infiltration of the by mutating the Ea promoter region, the protection from Langerhans' islets, a process called insulitis. The non-obese insulitis is disrupted.9 Three such promoter-mutated lines have diabetic (NOD) mouse provides a good model for human been previously described: the Sma58 (Sma) line has normal IDDM in that it resembles the human disease in pathophysio-E expression in the thymus but lacks peripheral expression on logy as well as in genetics.1 In both the mouse and man the B cells and is reported to have a reduced expression level on major histocompatibility complex (MHC ) class II seems to be macrophages;10 the WEDX21.16 (DX ) line has normal E the most important gene associated with susceptibility to or expression in the thymic medulla as well as on macrophages protection from IDDM.2 The NOD mouse has a pa...
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