Embodiments relate to peptide antagonists of ƴc-farnily cytokines, which is associated with important human diseases, such as leukemia, autoimmune diseases, collagen diseases, diabetes mellitus, skin diseases, degenerative neuronal diseases and graft-versus- host disease (GvHD). Thus, inhibitors of ƴc-cytokine activity are valuable therapeutic and cosmetic agents as well as research tools. Traditional approaches to inhibiting yc-cytokine activity involve raising neutralizing antibodies against each individual ƴc-cytokine family member/ receptor subunit. However, success has been limited and often multiple ƴc-cytokine family members co-operate to cause the disease state. Combinatorial use of neutralizing antibodies raised against each factor is impractical and poses an increased risk of adverse immune reactions. The present embodiments overcome these shortcomings by utilizing peptide antagonists based on the consensus ƴc-subunit binding site to inhibit ƴc-cytokine activity. Such approach allows for flexibility in antagonist design. In several embodiments, peptides exhibit Simul -Block activity, inhibiting the activity of multiple ƴc-cytokine family members.
