Antagonistic Effects of an Alternative Splice Variant of Human IL-4, IL-4δ2, on IL-4 Activities in Human Monocytes and B Cells☆

Abstract IL-4 is a pleiotropic cytokine which exerts its actions on various lineages of hematopoietic and nonhematopoietic cells. This cytokine is one of the central regulators of immunity in health and disease states. An alternative splice variant, in which the second of four exons is omitted, has been recently described and designated as IL-4δ2. The variant has been previously described as a potential naturally occurring antagonist of human IL-4 (hIL-4)-stimulated T cell proliferation. In this study, we investigated the effects of recombinant human (rh) IL-4δ2 on monocytes and B cells. In monocytes, rhIL-4δ2 blocked inhibitory action of hIL-4 on LPS-induced cyclooxygenase-2 expression and subsequent prostaglandin E 2 secretion. In B cells, rhIL-4δ2 was an antagonist of the hIL-4-induced synthesis of IgE and expression of CD23. Our results broaden the spectrum of hIL-4-antagonistic activities of rhIL-4δ2, thus creating the background for the potential use of rhIL-4δ2 as a therapeutic anti-hIL-4 agent.