INTERLEUKIN-2 INFUSION INDUCES HEMATOPOIETIC GROWTH-FACTORS AND MODIFIES MARROW REGENERATION AFTER CHEMOTHERAPY OR AUTOLOGOUS MARROW TRANSPLANTATION

Administration of interleukin 2 (IL2) to patients with minimal residual malignant disease following myeloablative chemo-radiotherapy may augment immune reconstitution and reduce the risk of relapse by increasing cytotoxic effector function and cytokine dependent killing directed at residual malignant cells. The ability of IL2 generated activated killer cells to inhibit haemopoietic progenitor cells and to release gamma-interferon (gamma-IFN) and tumour necrosis factor (TNF) may, however, retard haemopoietic recovery, as both TNF and gamma-IFN inhibit normal myelopoiesis in vitro. To determine the effect of IL2 infusion on myeloid regneration in vivo, we have examined haemopoietic recovery in patients receiving this cytokine following autologous marrow transplantation or ablative chemotherapy. We find that IL2 infusion accelerates neutrophil recovery and that granulocyte-macrophage colony stimulating factor (GMCSF) and IL3 mRNA become detectable in circulating mononuclear cells. Induction of TNF by IL2 may also contribute to subsequent acceleration of myelopoiesis by initiation of GM-CSF mRNA synthesis in patient marrow fibroblasts. These results show that IL2 infusion may facilitate myeloid recovery when administered during the period of haemopoietic regeneration following ablative chemoradiotherapy.