NEUTRALIZATION OF G-CSF INHIBITS ILK-INDUCED HETEROPHIL INFLUX - GRANULOCYTE-COLONY-STIMULATING FACTOR MEDIATES THE SALMONELLA ENTERITIDIS-IMMUNE LYMPHOKINE POTENTIATION OF THE ACUTE AVIAN INFLAMMATORY RESPONSE

Hematopoietic colony stimulating factors (CSF) regulate the growth and development of phagocytic cell progenitors and also augment functiona l activation of phagocytes, Granulocyte-CSF (G-CSF) is the CSF that ac ts specifically upon granulocyte progenitor cells and mature granulocy tes. We have shown that lymphokines (ILK) from T cells of birds immuni zed against Salmonella enteritidis (SE) induce a granulocytic (PMN) in flammatory response in chicks challenged with SE. This inflammatory re sponse was characterized by: (a) a dramatic emigration of granulocytic cells from the bone marrow into the peripheral blood, (b) an enhancem ent of the biological functions of the circulating PMNs, and (c) a dir ected influx of these activated PMNs to the site of bacterial invasion . In the current study, we determined the presence of G-CSF in ILK by Western blot analysis using a goat polyclonal antihuman G-CSF antibody (Ab). Using this Ab, we then evaluated the role of G-CSF in the ILK-i nduced protective inflammatory response in chickens against SE. Pretre atment of ILK with the Ab totally abolished the colony-stimulating act ivity of the ILK. Furthermore, Ab treatment of ILK resulted in: (a) an elimination of the ILK-induced peripheral blood heterophilia with a d ramatic inhibition of ILK-mediated protection against SE organ invasio n and (b) an elimination of accumulation of inflammatory PMNs in the p eritoneum with subsequent decrease in the survival rate of chicks chal lenged i.p. with SE. Taken together these studies demonstrate for the first time the contribution of G-CSF to avian PMN activation and the i mmunoprophylaxis of SE infection by ILK in neonatal chickens.