The Interleukin-1 System: Physiopathology and New Insights for its Therapeutical Potential

Abstract

Interleukin-1 (IL-1) is a family of polypeptides that is thought to play an important role in the regulation of the systemic response to invasive stimuli such as infection, trauma or antigenic challenge, exerting both immunopotentiating and inflammatory actions on a wide variety of cellular targets. Binding studies with radiolabeled IL-Is showed that structurally distinct receptors are present on different cell types, suggesting that the different biological activities might be the consequence of IL-1 binding to distinct receptor subtypes.

The highly detrimental activities of IL-1 represent a major drawback for its therapeutic application. Studies with IL-1 fragments have shown that the nonapeptide corresponding to the 163–171 sequence of human IL-1β is able to mimic the immunopotentiating activities of IL-1 while being devoid of its pro-inflammatory potentials, thus it might find clinical application as an immunostimulating agent. Since IL-1 is involved in some pathological conditions, strategies for anti-IL-1 therapy should also be developed. In this regard a recently characterized naturally occurring IL-1 receptor antagonist might play an important role and its structural relationships with IL-1β are hereafter discussed.