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 c ytokines in the regulation of hematopoiesis in vivo, we investigated H GFs and cytokine gene expression in appendices obtained from patients who underwent surgery for suspected appendicitis. Concomitantly, HGF g ene expression was studied in bone marrow (BM) biopsy specimens and pl asma HGF levels were measured. G-CSF gene expression was detected in i nflamed but not in normal appendices. With one exception, GM-CSF was d etectable in all appendices whether inflamed or not, whereas IL-3, exc ept for one case, was not expressed in appendices. None of the investi gated HGFs appeared to be expressed in BM biopsy specimens concurrentl y 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 i ncreased. Significant up-regulation of IL-8 and IL-6 gene expression w as observed in response to inflammation, in contrast to IL-1 alpha and IL-1 beta expression, which appeared not to be influenced by the infl ammatory 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.