An improved model for the examination of biological effects of locally administered cytokines.

Cytokines incorporated into agarose blocks and implanted subcutaneously into mice establish an in vivo gradient which can be used to mimic a local inflammatory process. We have developed a model in which cellular influx into cytokine impregnated blocks parallels the normal cellular reaction to infections or wounds. Agarose blocks containing supernatants from ConA activated rat spleen cells attracted neutrophils within 4 h. These cells were followed by lymphocytes and macrophages in 24 h. Flow cytometry analysis of lymphoid cells on day 1 revealed that 38% were Ig+ (B cell marker), 60% MAC-2,3+ and 20% Thy 1.2+ of which only a small fraction were expressing CD4 on their surface. These numbers changed with time following implantation of the blocks. Initially, isolated adherent cells (macrophages) were resting, with low phagocytic activity. Cells isolated from blocks at later time points were activated, as evidenced by their increased ability to ingest fluoresceinated beads. The secretion patterns of cells trafficking to murine rIL-1 containing agarose blocks were examined. TNF, IL-6 and antibody secreting cells were found. No IL-2 was detected at any time. We believe that this model will be of value in studies of local actions of cytokines.