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Cell death is a major endpoint in toxicologic assessment both in vivo and in vitro and numerous methods have become available for the characterization and quantitation of cell death. Recent developments in cell biology have made great strides in articulating two generally distinct modes ...

In response to the need to treat disorders such as Crohn’s disease, rheumatoid arthritis, allergies, and diabetes, the pharmaceutical industry has pursued the development of cytokines as therapeutic agents. Cytokines possess unique characteristics that are distinctly differe ...

In the United States, the association between drugs of abuse and increased risk of infection has been suspected since colonial times. More recent studies have confirmed this relationship for most commonly abused drugs. Studies in animal models and in human subjects indicate that this incr ...

Cytokines are polypeptide mediators produced by a variety of cell types that play crucial roles in immune and inflammatory responses. Genes that code for cytokines are highly polymorphic, and some of these polymorphisms directly or indirectly influence cytokine expression. The most ...

Exposure to airborne particles and gases including silica, asbestos, diesel exhaust, and ozone is associated with significant risk of pulmonary and cardiovascular morbidity and mortality. Increasing evidence suggests that macrophages and inflammatory mediators release ...

Many chemicals cause skin sensitization, resulting in allergic contact dermatitis, a delayed type hypersensitivity reaction. Chemical respiratory allergy is also an important occupational health problem, but there are currently available no validated methods for hazard id ...

The chemokine network, comprising cell surface G protein-coupled receptors and soluble small molecular-weight protein ligands, constitutes a highly evolved system that facilitates leukocyte recruitment in both innate and adaptive immunity. As such, it has attracted attenti ...

Flu-like reactions have been described, long before the introduction of therapeutic cytokines, in the clinical setting to treat a variety of pathological conditions. Indeed, flu-like reactions are commonly associated with vaccination as well as a number of infectious diseases unre ...

The vascular leak syndrome (VLS) is a major dose-limiting toxicity of cytokine therapy. VLS is characterized by an increase in vascular permeability resulting in tissue edema and, ultimately, multiple organ failure. The most frequent clinical manifestations of cytokine-induced V ...

A key component for the success of any therapeutic cytokine is the degree of immunogenicity mediated by the cytokine. There are many factors that can contribute to a cytokine being immunogenic, such as aggregation. The understanding of cytokine immunogenicity requires a thorough knowl ...

The identification of the role of cytokines in inflammatory and autoimmune diseases has led to significant progress in treatment. The best example is probably the beneficial effect of blocking TNFα in an increasing number of inflammatory diseases, starting with rheumatoid arthriti ...

The expression of cytochrome P450 and P-glycoprotein is altered during the operation of host defense mechanisms. The basis for this interaction is predominantly through cytokine-mediated pathways. Most of the major cytokines, including interleukin (IL)-1α, IL-1β, IL-2β, IL-6, tumor ...

The goal of cancer immunotherapy is to induce effective immune responses to malignant tumors. Immunostimulatory cytokines can promote antitumor immunity by augmenting immune responses to cancer cells and by reversing anergy and/or tolerance of immune effector cells. The clinic ...

Many clinical studies or case reports have focused on the clinical consequences of immunoenhancement or immune dysregulation mediated by therapeutic cytokines. Flu-like reactions, and the facilitation or exacerbation of inflammatory diseases, are the main consequences of im ...

Cytokines play a key role in modulation of immune responses. Cytokine networks regulate lymphocyte turnover, differentiation, and activation. Many different cell types, in addition to immune cells, produce cytokines and express receptors for cytokines. Cell-to-cell communic ...

Since the early 1990s, the measurement of cytokines has become an important tool to understand mechanisms of immunotoxicity as well as to identify and classify xenobiotics. During the past decade, several major scientific and technical developments have greatly increased the effic ...

Early events in an immune response stimulate the production of cytokines that direct the subsequent development of T-cells. The innate immune system initiates T-cell activation by inducing na�ve T-cells to differentiate into functional effector or memory T-cells. Effector T-cells p ...

Immunotoxins (ITs) are chimeric proteins consisting of an antibody linked to a toxin. The antibody confers specificity (ability to recognize and react with the target), whereas the toxin confers cytotoxicity (ability to kill the target) (1–3). ITs have been used in both mice and humans to elimin ...

The technological development and application of bispecific antibodies for biological research have advanced steadily since the idea of creating hybrid reagents with dual specificity was first promulgated by Nisonoff and Rivers (1). It was realized that appropriately designed ...

Liposomes are useful drug delivery vehicles since they may protect encapsulated drugs from enzymatic degradation and rapid clearance in vivo, or alter biodistribution, potentially leading to reduced toxicities (1,2). A major limitation to the development of many specialized app ...