Abstract 282 Poster Session I, Saturday, 5/1 (poster 151)

IL-3, IL-6, and IL-8 play an essential role in the immune response and effect a wide variety of leukocytes at different stages of differentiation. These proteins belong to a family of cyokines, many of which were first identified by their hematopoietic roles. Several family members (such as erythropoietin and granulocyte colony stimulating factor) have important non-hematopoietic effects in somatic tissues and in the central nervous system (CNS). The presence of a functional receptor is required for their biological activity. We hypothesized that the receptors for IL-3, IL-6 and IL-8 would be present in non-hematopoietic tissues in the developing human fetus. To test this hypothesis, we obtained organs (brain, spinal cord, eye, heart, lung, liver, spleen, adrenal, kidney, intestine, placenta and clavicle) from fetuses of 8 and 16 weeks post conception. Using specific primers to identify mRNA for these receptors, RT-PCR was performed on extracted RNA from the above tissues. To identify the specific cell types within each organ expressing these receptors, immunohistochemical localization was done using antibodies specific to human IL-3R, IL-6R, and IL-8Rβ. Additional brains ranging from 6 weeks to term gestation were evaluated for the presence of immunoreactivity. mRNA expression for IL-3R, IL-6R, and IL-8R was present in all organs tested. Cellular reactivity for IL-3R was limited to diffuse staining in the spleen and weak cell-specific staining in the glomeruli of the kidney. IL-6R reactivity was seen in a wide variety of tissues including liver, kidney, clavicle, lung, and neural tissues (neural retina, cerebral neurons, Purkinje cells, and choroid plexus). Staining for IL-8R revealed reactivity in liver, heart, lung, adrenal, kidney, placenta, and clavicle in addition to staining of the neural retina, neurons, and astrocytes in the brain. We conclude that although mRNA for IL-3R was present in many organs, the cellular immunoreactivity in non-hematopoietic cells was weak, with the exception of neurons and astrocytes in the CNS. In contrast to IL-3R, IL-6R and IL-8R immunoreactivity was identified in several organ-specific non-hematopoietic cells, including neurons and astrocytes. We speculate that interleukins 6 and 8 may have somatic effects that were previously unsuspected. We further speculate that IL-3, 6 and 8 may play a role in neurodevelopment. Further studies are needed to determine their specific function in the developing human CNS.