Molecules modulating immune/inflammatory responses, design and development of potential therapeutics

• Published in: Biotecnología aplicada Vol. 12; no. 2; pp. 101 - 102
• Main Authors: Arana, Manuel J, Santiago, Nelson, Chinea, Glay, Torres, Belkis, Pons, Tirso, Guerra, Maribel, Lopez, Eduardo, Callejo, M, Garay, Hilda E, Reyes, Osvaldo
• Format: Journal Article
• Language: English
• Published: Cuba Elfos Scientiae 31.12.1995
• ISSN: 0864-4551

The role of different bacteria-derived agents and cytokines on the onset and development of immune and inflammatory responses has been broadly studied. Gram-negative bacteria LPS binding to inflammatory cell membranes is related to the activation of a cytokine cascade constituting a central pathogenic mechanism on sepsis, and also related with activation of HIV replication in monocytes and acute graft-vs-host diseases. Therefore the design of anti-LPS molecules as drugs may be useful in the profilaxis and treatment of LPS-mediated diseases. At the same time, based on some natural proteins that function as cytokine antagonists maintaining basic structural features of receptor ligands, some groups have engineered cytokines to obtain both partial agonists or antagonists. Studies based on structure-activity analysis of IL/2/IL-2R interactions, indicating that binding and activation events can be' separated or modulated to elicit a subset of IL-2 responses excluding other, open the possibility to engineer IL-2 proteins with potential use as immunosupressing drugs (antagonist) or improved immunotherapeuticals (partial agonist). We briefly described herein preliminary results in using different approaches to obtain molecules modulating immune/inflammatory responses: (a) LPS neutralizing peptides, considering a charged cluster along the sequence of different LPS binding proteins, (b) IL-2 antagonists and partial agonists, using the phague displaying technology to expose hlL-2 and to select desired analogues obtained by random mutagenesis.