Cytokine Administration Alters the Distribution of Activated Lymphocytes to the Lung

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The effects of intraperitoneal injections of recombinant interleukin-1 alpha (IL-1; 250,000 U/day), interleukin-2 (IL-2; 50,000 units/day), interferon-gamma (IFN-gamma; 50,000 U/day) and tumor necrosis factor-alpha (TNF; 100,000 U/day), on the biodistribution of concanavalin A (Con A)-activated, indium-111-labeled lymphocytes were evaluated in BALB/c mice. Syngeneic spleen cells were activated for 48 h in medium with Con A (5 micrograms/ml) and maintained in culture for 72 h in IL-2 (1,000 U/ml). Groups of 12 mice were treated for 4 days with either one of the cytokines or saline. On day 4, mice received 10(7) lymphocytes (3-5 mu Ci) intravenously. Mice were sacrificed at 4 and 24 h following injection and the percent of administered dose per organ was determined. TNF and IL-1 produced a significant increase in lung uptake of radiolabeled lymphocytes at 4 and 24 h, whereas IL-2 and IFN-gamma decreased uptake at both time points. IL-1 increased uptake by liver at 4 and 24 h while IL-2 increased uptake only at 4 h. We conclude that the distribution of activated lymphocytes following adoptive transfer is altered by cytokines. This finding may have important implications for cell delivery during adoptive immunotherapy.