Cytokines categories

The therapeutic goal in autoimmune diseases such as RA is to control disease, to establish remission, and eventually to cure. In theory, this goal can be achieved using either Ag-specific approaches, for example, elimination of self-reactive T cells (assuming that a finite number of key Ags can be identified as the target of the autoimmune process in RA), or the non-Ag-specific approaches, for example, blockade of cytokines as in the case of TNF-a neutralization. Currently, only the latter types of approaches have yielded clinical benefit, and it is in this category that approaches to block chemokines or receptors may be included. Despite their appeal in terms of effectiveness, non-Ag-specific approaches carry a higher risk of immunosuppression and opportunistic infections (48). 

Mammalian cell culture is more technically complex and more expensive than microbial cell fermentation. Therefore, it is usually only used in the manufacture of therapeutic proteins that show extensive and essential post-translational modifications. In practice, this usually refers to glycosylation, and the use of animal cell culture would be appropriate where the carbohydrate content and pattern are essential to the protein s biological activity, its stability or serum half-life. Therapeutic proteins falling into this category include EPO (Chapter 10), the gonadotrophins (Chapter 11), some cytokines (Chapters 8-10) and intact monoclonal antibodies (Chapter 13). 

The cytokine family continues to grow, and often a decision to include a regulatory protein in this category is not a straightforward one. The following generalizations may be made with regard to most cytokines ... 

Membranes cast upon glass slides also fall into the 3D surface category. Most notable are the nitrocellulose-coated FAST slides offered by Schleicher Schuell (S S) BioScience. A cytokine micro-ELISA product xmder the trade name Provision has been introduced in single-slide and 96-well spacing (64 usable wells) formats. It is called FAST Quant (Harvey, 2003). Historically, nitrocellulose membrane has been used for the sequestering of both proteins and nucleic acids. The adaptation by S S of this microporous (0.2-p pores) material cast into a microarray format has been relatively straightforward. 

Drug categories discussed in this part of the book include hematopoietic growth and coagulation factors (Chapter 6), interferons and cytokines (Chapter 7), hormones (Chapter 8), enzymes (Chapter 9),... 

Proliferative assays may be grouped into four basic categories survival [e.g., IL-2 assay (G4)], mitogenesis [e.g., GM-CSF assay using TF-1 cell lines (K4)], comitogenesis [e.g., thymocyte assay for IL-1 (G3)], and colony formation [e.g., assay of hematopoietic cytokines (M20)]. 

The primary purpose of the endocrine system is to maintain homeostasis — that is, to maintain a relatively constant internal environment in the face of a constantly changing external environment. The endocrine system consists of hormones and the glands and tissues that produce the hormones. A hormone is a chemical substance released by certain cells to effect the function of other distant cells (endocrine function). Many compounds act as endocrine hormones as well as having paracrine and autocrine functions. Paracrine and autocrine describe actions on nearby cells and on other cells that produce the substance, respectively. There is considerable overlap between substances classified as hormones and other chemical messengers such as neurotransmitters and cytokines. Many substances function in more than one of these categories. For example, epinephrine and norepinephrine function as both neurotransmitters and adrenal medullary hormones. 

Among the most highly selective cytokine biopharmaceuticals are the interferons. Interferons are members of a large family of related proteins that may be divided into two categories type I and type II interferons. Type I interferons (i.e., a- and P-interferon) possess antiviral and anti-proliferative properties, whereas type II interferons (i.e., y-interferon) have immunostimulatory activity. Several animal species were examined for their responsiveness to interferons, and with the exception of nonhuman primates, all tested animal species were found to be unresponsive [15]. 

As with bacteria, fungal virulence factors can be divided into two main categories virulence fectors that facilitate infection and virulence factors that affect the host. Virulence factors that promote adherence to host cells and fecilitate fungal invasion include capsule production to inhibit phagocytosis and cytokines to depress the host immune system. Multiple virulence fectors target the host, such as cell wall polysaccharides that activate the complement cascade and provoke an inflammatory reaction or the secretion of cytokines and mycotoxins that directly damage host tissues. 

Those cytokines which are generally permissive or inhibitory for antibody production by B lymphocytes and may influence the secretion of a number of different antibody isotypes, depending on which of the specific stimuli are present. These cytokines include IL-2, IL-5, IL-6 and IFN7 (but this is not an exhaustive list). Permissive stimuli other than cytokines, for example the co-stimulatory signals delivered by T lymphocytes, may also be included in this category. 

Indications Rheumatoid arthritis Category Cytokine inhibitor TNF inhibitor Half-life 10-20 days... 

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