ENHANCEMENT IN-VITRO OF THE LOW INTERFERON-GAMMA PRODUCTION OF LEUKOCYTES FROM HUMAN NEWBORN-INFANTS

Interferon-gamma (IFN-gamma), a lymphokine produced by lymphocytes wit h the help of monocytes, is essential for host resistance to intracell ular pathogens. Leukocytes from normal term newborn infants cannot pro duce IFN-gamma in vitro in response to stimulation by antigen or mitog ens in vitro or in vivo. We investigated the production of IFN-gamma i n vitro using endotoxin from Salmonella typhimurium as a stimulus. In contrast to those from adults, mononuclear cells derived from the cord blood of newborn infants did not produce IFN-gamma in response to thi s endotoxin. We investigated the contribution of the functional immatu rity of cord blood monocytes to this relative inability to produce IFN -gamma. Aging of the monocytes for 2 weeks in vitro or treatment of fr eshly isolated cord blood monocytes with conditioned medium (from cult ures of mononuclear cells from healthy adults) greatly enhanced IFN-ga mma production stimulated by endotoxin. Furthermore, recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), or IFN-gamma was able to substitut e in part for the conditioned medium from adult cells. Thus correction of the functional immaturity of monocytes derived from newborn infant s can result in enhanced production of IFN-gamma in vitro.