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.
Department of Medicine, Massachusetts General Hospital, Boston.
S M
SM
Dubinett
R J
RJ
Callahan
W J
WJ
Xia
M
M
Ahmad
H W
HW
Strauss
R L
RL
Kradin
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