Extramedullary hematopoietic growth factor and cytokine gene expression indicate endocrine regulation of hematopoiesis in patients with acute appendicitis

To analyze the role of hematopoietic growth factors (HGFs) and other cytokines in the regulation of hematopoiesis in vivo, we investigated HGFs and cytokine gene expression in appendices obtained from patients who underwent surgery for suspected appendicitis. Concomitantly, HGF gene expression was studied in bone marrow (BM) biopsy specimens and plasma HGF levels were measured. G-CSF gene expression was detected in inflamed but not in normal appendices. With one exception, GM-CSF was detectable in all appendices whether inflamed or not, whereas IL-3, except for one case, was not expressed in appendices. None of the investigated HGFs appeared to be expressed in BM biopsy specimens concurrently obtained with the appendices. Plasma G-CSF levels were significantly elevated in patients with appendicitis compared with patients without inflamed appendices. Circulating levels of GM-CSF and IL-3 were not increased. Significant up-regulation of IL-8 and IL-6 gene expression was observed in response to inflammation, in contrast to IL-1 alpha and IL-1 beta expression, which appeared not to be influenced by the inflammatory state. These data indicate that G-CSF, and not GM-CSF or IL-3, is essential for the regulation of inducible granulopoiesis in acute inflammatory conditions, and that G-CSF acts in an endocrine fashion.