Interleukins, generally

Rapamycin has been known for many years to possess immunosuppressive activity by interfering with the activation of B- and T-cells by interleukin-2. Indeed the first clinically approved indication for rapamycin was renal transplantation. Currently, rapamycin and RAD001 also show promise in liver transplantation and cardiac transplantation, respectively. Generally, treatment protocols utilize a combination of an mTORCl inhibitor, a calcineurin inhibitor and steroids to optimize immunosuppression and minimize nephrotoxicity and other side effects. Rapalogs are also... 

The first report of the action of a chemokine on neurons was published in 1993. The study demonstrated that IL-8 could increase the survival of cultured neurons (Araujo and Cotman, 1993). However, as can be appreciated from its name, IL-8 was not known to be a chemokine at that time and was instead classed as an interleukin. Indeed, the expression of chemokine receptors by neurons was not generally appreciated until around 1997/1998 when several reports suggested this. These reports included observations of the expression of chemokine receptors by neuronal cell lines (Hesselgesser et al. 1997), primary cultures of neurons (Meucci et al. 1998 Ohtani et al. 1998), and in brain sections from HlV-1, Alzheimer s disease, and other patients (Horuk et al. 1997 Westmoreland et al. 1998 Xia et al. 1997). Furthermore, data were obtained, suggesting functions for chemokine signaling in the development of the nervous system (Zou et al. 1998) as well as in neuronal survival and communication (Giovannelli et al. 1998 Meucci et al. 1998). 

Table 5.2. Some interleukin preparations approved for general medical use (or in clinical trials) and the disease(s) for which they are indicated. The developing company is also listed. The drug status refers to its status in the USA...

Anakinra is the first biologic drug that has been developed specifically as an interleukin (IL)-l receptor antagonist and is derived from an endogenous IL-IRa. The drug blocks the activity of IL-1 in synovial joints, reducing the infiammatory and joint destructive processes associated with rheumatoid arthritis. It is administered subcutaneously and is generally well tolerated. Injection-site reactions are the most commonly reported adverse event. 

Cytokine is a general term used for a diverse assortment of water-soluble protein molecules that mediate interactions between the various cells of the innate and adaptive immune systems. Over 100 human cytokines are currently under study and more than 300,000 research papers have been published in this area over the past 10-15 years. The interferons, discussed in section 6.2.1, are a subset of the cytokines, as are the interleukins, discussed in section 6.1.3. The nomenclature used to describe cytokines is somewhat confusing and varying subclasses of cytokines are recognized ... 

A. General description Denileukin dif-titox is a recombinant, DNA-derived, interleukin-2 receptor specific ligand, cytotoxic fusion protein consisting of diphtheria toxin fragments A and B fused to interleukin-2. It is produced by expression of a recombinant fusion protein in Escherichia coli that contains nucleotide sequences for human interleukin-2, and sequences for the enzymatically active fragment A of diphtheria toxin and the membrane-translocating portion of diph-... 

A. General description Anakinra is a recombinant nonglycosylated form of the human interleukin-1 receptor antagonist (IL-lRa). It differs from native human IL-lRa by the addition of a methionine residue at its amino terminus. Anakinra consists of 153 amino acids and has a molecular weight of 17.3 kDa. It is produced... 

The authors of the last report commented that generalized delayed type hypersensitivity to systemic administration of a glucocorticoid is rare. Despite the potent immunosuppressive effect of glucocorticoids on immunocompetent cells, the clinical features, the skin biopsy specimen, and the positive delayed skin test reactions strongly suggested an immunological mechanism T cells were clearly involved and the high concentrations of interleukins 5, 6, and 10 were consistent with a T helper type 2 reaction. The raised concentrations of interleukin-5 were probably responsible for the blood and tissue eosinophilia. 

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