Aspirin in Immunotherapy : Old molecule - even newer tricks

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Aspirin in Immunotherapy

Aspirin in Immunotherapy

A spirin (N-acetylsalicylic acid, ASA) is known since more than 100 years, but does not stop to surprise with new application options. A few years ago the influence of Aspirin on the immune system was recognized. Aspirin is able to induce tolerance in regulatory T cells by inhbition of interleukin 4 gene transcription and, at higher concentrations even the central nuclear regulation “switch” NF-kappa B.

The concentrations for inhibition (IE50) of certain molecules are: COX-1: 0.3 µg/ml; COX-2: 50 µg/ml; IL-4: 180 µg/ml; NF-kB: 1800 µg/ml.

With the standard daily dose of aspirin in case of acute fever you can expect to reach a serum concentration that will work perfectly for COX-1 and COX-2, the main targets of aspirin – but not efficently inhibit IL-4.

Studies showed that you can reach appropriate serum concentrations with very high aspirin doses taken over longer time. However, such high doses significantely increases the risk of serious side effects like stomach bleeding or tinnitus. In addition, aspirin taken orally is resorbed into systemic circulation at only approximately 63%. Aspirin is also adsorbed on human serum albumin, extending its half-life and distribution but reducing the effective concentration.

That is why PLS-Design developed a local inhibition approach, bringing the drug at higher concentration to the site of immune reaction. Our hydrogel relase system provides a constant high concentration over the necessary time to induce tolerance reaction and modulate T cells. These primed cells will move from the reaction site into the whole body and change the systemic immune reaction. The local high drug concentration will not cause significant side reactions as it will be metabolized or simply diluted in the body circulation.

Read more about local immune modulation click here
Read more about multi-level tolerance induction click here

Reference: Cianferoni et al. 2001, Selective inhibition of interleukin-4 gene expression in human T cells by aspirin, Blood 97:1742-1749.
Reference: Gibson et al. 1975, Kinetics of Salicylate Metabolism. Br. J. Clin. Pharm. 2:233-238.

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