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Third-party-funded project

Interleukin -5 antagonists

Project management at the University of Würzburg:

Participating scientists:

1L-5 (lnterleukin-5), also called EDF (eosinophile difterentiation factor), functions as an
important effector cytokine during a Th2-dominated immune response. IL-5 induces the
development and activation of eosinophilic granulocytes, an therefore is crucial for
intlammatory processes associated with general immunity. This cytokine also exerts a
pathophysiological role during atopic diseases as e.g. allergic asthma. IL-5 is one of the small
4-helix-bundle cytokines. The homodimeric protein provides one high-affinity binding site for
the specific interaction with the IL-5 receptor a chain. As a second essential receptor
component functions the common ßc chain which is involved also in IL-3 and GM-CSF
signaling. The aim of the present project is to determine the functional IL-5 epitope for ßc
interaction by analysing "loss-ot--function" and "mismatch" mutant proteins of IL-5. Previous
experiments with IL-4 [ 1,2] resulted in the identitlcation of crucial side chains and allowed
the construction of selective IL-4 agonists and antagonists. Corresponding IL-5 variants will
be valuable tools tor the development of anti-eosinophile and anti-asthma drugs.
[1] F. Letzelter, Y. Wang and W. Sebald (1998) Eur. J. Biochem. 257, 11-20.
[2] T. Hage, W. Sebald and Reinemer P. (1999) Ce1197, 271-281.

Key words:

Projekt period: from 01.2002 to 12.2002

Funding institution:
DFG ,Granting date: 23.07.1999