Antagonistic effects of an alternative splice variant of human IL-4, lL-4 delta 2, on IL-4 activities in human monocytes and B cells

IL-4 is a pleiotropic cytokine which exerts its actions on various lineages of hematopoietic and nonhematopoietic cells. This cytokine is one of the c entral regulators of immunity in health and disease states. An alternative splice variant, in which the second of four exons is omitted, has been rece ntly described and designated as IL-4 delta 2. The variant has been previou sly 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-4 delta 2 on monocytes and B cells. In monocytes, rhIL-4 delta 2 blocked inhibitory action of hIL-4 on LPS-induce d cyclooxygenase-2 expression and subsequent prostaglandin E-2 secretion. I n B cells, rhIL-4 delta 2 was an antagonist of the hIL-4-induced synthesis of IgE and expression of CD23. Our results broaden the spectrum of hIL-4-an tagonistic activities of rhIL-4 delta 2, thus creating the background for t he potential use of rhIL-4 delta 2 as a therapeutic anti-hIL-4 agent. (C) 1 999 Academic Press.