Ubiquitous transgenic expression of the IL-23 subunit p19 induces multiorgan inflammation, runting, infertility, and premature death

p19, a molecule structurally related to IL-6, G-CSF, and the p35 subunit of IL-12, is a subunit of the recently discovered cytokine IL-23. Here we sho w that expression of p19 in multiple tissues of transgenic mice induced a s triking phenotype characterized by runting, systemic inflammation, infertil ity, and death before 3 mo of age. Founder animals had infiltrates of lymph ocytes and macrophages in skin, lung, liver, pancreas, and the digestive tr act and were anemic. The serum concentrations of the proinflammatory cytoki nes TNF-alpha and IL-1 were elevated, and the number of circulating neutrop hils was increased. In addition, ubiquitous expression of p19 resulted in c onstitutive expression of acute phase proteins in the liver. Surprisingly, liver-specific expression of p19 failed to reproduce any of these abnormali ties, suggesting specific requirements for production of biologically activ e p19. Bone marrow transfer experiments showed that expression of p19 by he mopoietic cells alone recapitulated the phenotype induced by its widespread expression, pointing to hemopoietic cells as the source of biologically ac tive p19. These findings indicate that p19 shares biological properties wit h IL-6, IL-12, and G-CSF and that cell-specific expression is required for its biological activity.