Interleukin-1 production following T-cell-depleted and unmodified marrow grafts

Abstract

Interleukin-1 (IL-1) production by endotoxin-stimulated cultured monocytes from 31 participants in grafts of marrow depleted of mature cellular elements by treatment with soybean agglutinin and sheep red blood cells (SBA-E-) and 12 recipients of unfractionated bone marrow were studied and compared with normal controls. Patients were studied prior to marrow transplant (BMT) and at 1 month, 2 to 4 months, and 5 to 6 months post-transplant. Deficiencies in IL-1 production (<50 units) were detected in both transplant groups prior to and at 1 month post-BMT. From 2 to 4 months post-transplant, 67% of the recipients of unmodified marrow and 45% of the recipients of SBA-E- marrow grafts produced a normal level of IL-1. By 5 to 6 months post-transplant and thereafter, the proportions of patients exhibiting deficiencies in IL-1 production in each group were equally low. We also evaluated the impact of early deficiencies of IL-1 on engraftment, hematopoietic function, and immunological reconstitution. Deficiencies in IL-1 production persisting to 2 to 4 months post-BMT did not significantly affect the degree of chimerism or the time to recovery of neutrophil counts to 500/mu l in recipients of either unmodified or T-cell-depleted marrow. Platelet recovery during the first 50 days post-transplant was significantly slower in the IL-1-deficient group, but thereafter rebounded, so that by 4 months post-BMT patients with initial deficiencies in IL-1 production achieved levels comparable with those attained by patients with normal production of IL-1. When we looked at the lymphocyte response to phytohemagglutinin (PHA), there was no difference detected among patients with or without IL-1 deficiency receiving unmodified transplants. In contrast, recipients of T-cell-depleted grafts exhibiting a prolonged deficiency of IL-1 experienced a slower rate of recovery of PHA responses. Our results suggest that IL-1 may play an important role in the early expansion of megakaryocytic precursors following an allogeneic marrow transplant and may facilitate the functional development of allogeneic lymphoid progenitors following a T-cell-depleted marrow graft.