Interleukin-1 is identical to hemopoietin-1: studies on its therapeutic effects on myelopoiesis and lymphopoiesis.
Conditioned medium from the human tumor cell line HBT 5637 possesses a unique hematopoietic activity, originally termed hemopoietin-1. Hemopoietin-1 alone does not stimulate bone marrow colony formation or proliferative responses in vitro, but rather potentiates responses to other hematopoietic growth factors, such as CSF-1 and GM-CSF. In studies designed to characterize the molecular nature of this factor, it was found by molecular, biochemical biological and serological criteria that all the hemopoietin-1 like activity could be attributed to IL-1 alpha. The therapeutic potential of IL-1 was then tested in a system where myelopoiesis is depressed by whole body irradiation. After 750 R irradiation, mice were administered IL-1 twice daily for the duration of the experiment. Mice which received IL-1 treatment had an accelerated recovery of marrow colony forming capacity which was also reflected by significantly higher blood neutrophil levels as compared to control irradiated mice. IL-1 treated irradiated mice also had a significant increase in resistance to bacterial challenge 14 days post irradiation. Thus, IL-1 treatment was effective in augmenting myelopoiesis following sublethal whole body irradiation. The effects of the IL-1 treatment on the recovery of lymphocyte numbers was also assessed. Here the IL-1 treated irradiated mice had fewer lymphocytes and depressed mitogen responses by spleen cells. Indeed the thymus of the IL-1 treated irradiated mice remained chronically hypoplastic for the duration of the experiment. Although IL-1 treatment increased myeloid progenitors in the bone marrow, it caused a decrease in the frequency of pre-B cells. Thus, IL-1 administration is an effective treatment for accelerating myeloid recovery following the cytoreductive effects of irradiation, but the myelopoietic augmentation may be at the expense of lymphoid recovery.
Morrissey
P J
PJ
Immunex Corporation, Seattle, WA 98101.
Mochizuki
D Y
DY
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000502:physiology; D006133:Growth Substances / Q000494:pharmacology* / Q000627:therapeutic use; D006410:Hematopoiesis / Q000187:drug effects; D016298:Hematopoietic Cell Growth Factors; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology* / Q000627:therapeutic use; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology
D006133:Growth Substances; D016298:Hematopoietic Cell Growth Factors; D007375:Interleukin-1