TUMOR NECROSIS FACTOR, MACROPHAGE COLONY-STIMULATING FACTOR, AND INTERLEUKIN 1 PRODUCTION WITHIN SPONGE MATRIX ALLOGRAFTS1

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Abstract
Neither the presence nor the specific role of secretory cytokines in in vivo allograft rejection has been extensively studied. We quantitated the levels of colony-stimulating factors, tumor necrosis factor, and interleukin 1 within the rejecting allograft. BALB/c (H-2d) mice were implanted with polyurethane sponges containing either allogeneic C57BL/6 (H-2b) or syngeneic splenocytes. or splenocyte-free media. At various days postgrafting, the sponges were harvested, and the cells infiltrating the grafts were analyzed for specific antidonor cytolytic activity, while IL-1, TNF, and CSF levels were measured in the graft exudate fluid. Allogeneic grafts had significantly higher concentrations of CSF, TNF, and IL-1 than syngeneic of splenoeyte-free grafts. A speeific radioimmunoassay revealed that macrophage colony-stimulating factor (M-CSF) is the primary CSF produced in the grafts. Peak TNF levels preceded peak M-CSF and IL-1 levels, which coincided with the initial appearance of allospecific cytotoxic T lymphocytes. Maximal CTL activity was seen on day 13, when the levels of these cytokines had already hegun to fall. Specific bioassays for multi-CSF (IL-3), granulocyte CSF, granulocyte-macrophage CSF, IL-2, and IL-4 failed to detect these eytokines in the sponge fluid at any time. We hypothesize that TNF, M-CSF, and IL-1 probably play regulatory roles in the immunologic events at the site of allograft challenge.