Interleukin susceptibility

Besides direct apoptosis effectors, there are a number of other diugs which influence the above explained apoptosis pathways more indirectly. This class of diugs includes molecules which inhibit survival pathways like e.g. the Ras/Raf kinase pathway, the NF-kB pathway and many others. Also inhibitors of survival cytokines which are sometimes produced by cancer cells in an autocrine fashion can render cells susceptible to apoptosis and, hence, effective cancer therapy. These include, but are not limited to, ligands for dependence receptors and cytokines like e.g. interleukin-4. 

Pung, O.J., Tucker, A.N., Yore. S.J. and Luster, M.L (1985). Influence of estrogen on host resistance Increased susceptibility of mice to Listeria monocytogenes correlates with depressed production of interleukin 2. Infect. Immun. 50 91-96. 

Recent studies showed that rituximab down-regulates interleukin-10 (lL-10) in some lymphoma cell lines (17,18,19,20,21,22,23,24,25,26,27). IL-10 has a stimulatory function as an autocrine or paracrine growth factor for lymphoma cells (28). lL-10 is a known promoter of BCL2 expression in hematopoietic cells (29) as well as lymphoma cells (28). Rituximab is known to induce down-regulation of lL-10 expression and consequently of bcl-2 protein expression, making B-cells more susceptible to apoptotic signals (Fig. 1) (30,31,32). However, the implication of lL-10 on clinical outcome after rituximab therapy is still unclear. 

Smith, J.R., Hart, P.H., Coster, D.J., Williams, K.A. Mice deficient in tumor necrosis factor receptors p55 and p75, interleukin-4, or inducible nitric oxide synthase are susceptible to endotoxin-induced uveitis, Invest. Ophthalmol. Vis. Sci. 1998, 39, 658-661. 

Cranath, W.O. Jr, Connors, V.A. and Tarleton, R.F. (1 994) Interleukin 1 activity in haemolymph from strains of the snail Biomphalaria glabrata varying in susceptibility to the human blood fluke, Schistosoma mansoni presence, differential expression, and biological function. Cytokine 6, 21-2 7. 

Ducreux, S., Zorzato, F., Muller, C., Sewry, C., Muntoni, F., Quinlivan, R., Restagno, G., Girard, T., and Treves, S. (2004). Effect of Ryanodine Receptor Mutations on Interleukin-6 Release and Intracellular Calcium Homeostasis in Human Myotubes from Malignant Hyperthermia-Susceptible Individuals and Patients Affected by Central Core Disease. J Biol Chem 279(42) 43838 16. 

Ober C, Leavitt SA, Tsalenko A, et al Variation in the interleukin 4-receptor alpha gene confers susceptibility to asthma and atopy in ethnically diverse populations. Am J Hum Genet 2000 66 517-526. (Ill)... 

Santhanam, U., Ray, A. and Sehgal, P.B. (1991) Repression of the interleukin 6 gene promoter by p53 and the retinoblastoma susceptibility gene product. Proc. Natl. Acad. Sci. USA 88 7605-7609. 

Interleukin-1 polymorphisms have been associated with increased risk of gastric and may influence the varying susceptibility to develop gastric cancers and chromosome 18q loss is connected to vascular invasion. ... 

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