Immunotherapy in Patients with Systemic MycosesFarmaki, Evangelia; Roilides, Emmanuel
doi: 10.2165/00063030-200115040-00001pmid: 11437686
Evidence from several in vitro and animal model studies suggests a modulatory role of haemopoietic, TH1 and TH2 cytokines in host defence against fungi, and highlights their potential utility as adjunctive therapy for management of systemic mycoses (SM). However, there are limited clinical data to support the use of cytokines in prevention and treatment of SM. Thus, at present no adjunctive treatment is justified for routine use in all patients. Potential application of these immunomodulatory agents include the use of granulocyte-macrophage colony-stimulating factor or macrophage colony-stimulating factor in the management of mycoses in neutropenic patients with myelogenous leukaemia or bone marrow transplantation. Interferon-γ may have a useful role against aspergillosis in patients with chronic granulomatous disease. Granulocyte colony-stimulating factor-elicited white blood cell transfusions may be life saving to patients with refractory SM. Better understanding of synergy between cytokines and specific antifungals may provide powerful tools for managing these serious infections.
ImmunoliposomesBendas, Gerd
doi: 10.2165/00063030-200115040-00002pmid: 11437687
Immunoliposomes (antibody-coupled liposomes) have been regarded as very attractive drug-targeting systems for chemotherapeutic cancer treatment. Fundamental problems regarding immunoliposome preparation and application such as antibody coupling and immunoliposome stability and pharmacokinetics have been overcome during the last decade. Therefore, several promising studies on tumour targeting have been described in recent years. Adding to existing reviews on liposomal drug delivery, this article focuses on immunoliposome tumour targeting and summarises various experiments of immunoliposome application in vitro and in vivo with respect to structural liposomal parameters, therapeutic potential and the requirements of the target sites. New therapeutic trends related to immunoliposomes are also considered. Remaining problems in immunoliposome application, especially immunological aspects, are discussed, as are strategies that might help to overcome these obstacles.
Comparative Efficacy of Inhaled Corticosteroids and Antileukotriene Drugs in AsthmaSmith, Lewis
doi: 10.2165/00063030-200115040-00004pmid: 11437689
Asthma is an inflammatory disease of the airways that is best treated by minimising exposure to factors that provoke the inflammation (e.g. allergens) and by administering drugs that reduce the inflammatory response. The cornerstone of asthma treatment is inhaled corticosteroids. Their effectiveness is a result of their potent and broad anti-inflammatory properties. Antileukotriene drugs (leukotriene modifiers) provide an alternative and novel approach to the treatment of asthma. The novelty of these new compounds is that their effectiveness is firmly based on the pathophysiology of asthma, specifically the role played by the cysteinyl leukotrienes. At the same time, the availability of the antileukotriene drugs has stirred debate over when they should be used and how they compare to inhaled corticosteroids. Although the answers are not fully known at this time, the currently available published and presented data are adequate for us to draw some conclusions about their relative effectiveness and role in asthma treatment. The antileukotriene drugs are more effective than placebo, but they are not as effective as inhaled corticosteroids in improving lung function [measured as the forced expiratory volume in 1 second (FEV1) or peak expiratory flow rate (PEFR)], reducing β2-agonist use, and decreasing symptom-free days. In contrast, they may have similar beneficial effects on reducing asthma exacerbations and decreasing peripheral blood eosinophil counts. In the absence of knowing a priori the response of an individual patient to treatment with either therapy, the data favour initiating treatment with an inhaled corticosteroid. However, for patients with mild to moderate disease there are a number of circumstances that support using an antileukotriene drug first. A few examples are aspirin intolerance, predominantly exercise-induced symptoms and problems with using an inhaler or the adverse effects of inhaled corticosteroids such as dysphonia and thrush. For patients with more severe disease, inhaled corticosteroids remain the treatment of choice. Antileukotriene drugs should be considered as add-on therapy, especially in view of their possible complementary effects on reducing airway inflammation.
Tumour Necrosis Factor-α Blockers in Rheumatoid ArthritisRichard-Miceli, Corinne; Dougados, Maxime
doi: 10.2165/00063030-200115040-00005pmid: 11437690
Tumour necrosis factor (TNF)-α has been found to play a central role in the pathogenesis of rheumatoid arthritis, leading to development of novel drug therapies that neutralise the deleterious effects of this cytokine. This new concept of immunobiological treatment of rheumatoid arthritis has yielded successful results. Although the 2 currently available TNFα blockers, infliximab and etanercept, differ in structure, mechanism of action and pharmacokinetics, they have provided similar benefits both in clinical improvement and in slowing and even arresting the progression of radiographic damage. This therapeutic response seems to be unequalled by ‘conventional’ treatments in rheumatoid arthritis, and is incontestably a turning point in the therapeutic management of this disease.