Cytokine administration alters the distribution of activated lymphocytes to the lung.
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.
Dubinett
S M
SM
Department of Medicine, Massachusetts General Hospital, Boston.
Callahan
R J
RJ
Xia
W J
WJ
Ahmad
M
M
Strauss
H W
HW
Kradin
R L
RL
D000818:Animals; D016207:Cytokines / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D007375:Interleukin-1 / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D007376:Interleukin-2 / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000502:physiology; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma