Characterising vancomycin's immunotoxic profile using Swiss and CFW mice as an experimental model.
ABSTRACT Immunotoxicology can lead to determining the adverse effects of different compounds on the immune system. Sometimes, many drugs (especially antibiotics) induce immune alterations, mainly auto-immunity. This study was aimed at determining vancomycin's immunotoxic effect by comparing the original molecule to two of the most used copies. Thirty-two mice from two murine strains (Swiss and CFW) were treated with three antibiotic formulations for studying its effect on splenic lymphoid and peripheral blood cell populations by using haemograms, flow cytometry and blastogenesis assays. The results indicated that vancomycin produces neutropenia and lymphocytosis in peripheral populations and that it induces a selective immunomodulatory effect on splenocyte sub-populations, depending on formulation and the strain so treated.
Article: Drug-induced autoimmunity.[show abstract] [hide abstract]
ABSTRACT: Drug induced autoimmune syndromes have been recognized for many years. The classical presentation is that of drug-induced lupus, a generally milder version of the idiopathic disorder that is associated with production of antihistone antibodies. This pattern is now changing, in part due to the many new drugs that have been introduced into clinical practice for treatment of autoimmune diseases, including both conventional pharmaceuticals and biologicals. The number and complexity of drug-induced autoimmune syndromes has increased, and many are now associated with autoantibodies that have been classically defined as limited to idiopathic disease states. Furthermore, some of these drug-induced syndromes have life-threatening complications, so that recognition of drug-induced disease has become more difficult at a time when it is more urgent to establish a correct diagnosis. Many reports are limited to case descriptions, and few controlled investigations have been carried out. Nevertheless, it is possible to derive an approach to considering possible mechanisms by which these processes may take place. This chapter will consider these proposed mechanisms, using some of the implicated drugs to illustrate possible pathogenetic pathways.Bailliè re s Best Practice and Research in Clinical Rheumatology 11/2004; 18(5):677-88. · 3.55 Impact Factor
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ABSTRACT: The immunotoxic effects of drugs are divided into immunosuppression, immunostimulation, hypersensitivity and autoimmunity. The major adverse consequences of immunosuppression are infectious complications and virus-induced malignancies. Flu-like reactions, more frequent autoimmune diseases and hypersensitivity reactions to unrelated allergens, and inhibition of drug-metabolising enzymes are the adverse effects related to immunostimulation. Hypersensitivity reactions are the most frequent immunotoxic effects of drugs. They include immune-mediated ('allergic') and non immune-mediated ('pseudoallergic') reactions. Drug-induced autoimmune reactions, either systemic or organ-specific, are seemingly rare. A review of drug-induced immunotoxic effects demonstrates that immunotoxicity is a significant cause of morbidity and even mortality. As immunotoxicologists have long focused on immunosuppression, the nonclinical immunotoxicity safety assessment of unexpected immunosuppression is based on a number of relatively well standardised and validated animal models and assays. However, there is no general consensus regarding the minimal requirement for this assessment. Many different assays can be used to extend the assessment case by case. Few animal models and assays have been validated for use in the nonclinical safety assessment of unexpected immunostimulation. The situation is worse regarding the prediction of hypersensitivity and autoimmune reactions. Our limited understanding of the molecular and cellular mechanisms of immunotoxicity accounts, at least partly, for this situation. Recent guidelines for the immunotoxicity safety assessment of drugs, even though conflicting on several points, will serve as an impetus not only to refine current animal models and assays, but also to search for better alternatives. The new data generated will have to be interpreted and extended to animal species other than just rodents. Likewise, animal results will have to be compared with findings in humans. The search for immunological endpoints that can be used in several animal species and in humans will therefore become essential. Specific endpoints and clinical criteria that can be included in clinical trials to further investigate the potential for immunotoxicity of new drugs will have to be defined. Because immunotoxicity plays a key role in drug-induced adverse effects, the role of immunotoxicology in drug safety assessment is indisputable and the systematic nonclinical as well as clinical immunotoxicity assessment of every new drug is deemed essential.Drug Safety 02/2005; 28(2):127-36. · 3.41 Impact Factor
Article: Red man syndrome.[show abstract] [hide abstract]
ABSTRACT: Vancomycin can cause two types of hypersensitivity reactions, the red man syndrome and anaphylaxis. Red man syndrome has often been associated with rapid infusion of the first dose of the drug and was initially attributed to impurities found in vancomycin preparations. Even after improvement in vancomycin's purity, however, reports of the syndrome persist. Other antibiotics (e.g. ciprofloxacin, amphotericinB, rifampicin and teicoplanin) or other drugs that stimulate histamine release can result in red man syndrome. Discontinuation of the vancomycin infusion and administration of diphenhydramine can abort most of the reactions. Slow intravenous administration of vancomycin should minimize the risk of infusion-related adverse effects.Critical Care 05/2003; 7(2):119-20. · 4.93 Impact Factor