Interleukin 1-induced augmentation of experimental metastases from a human melanoma in nude mice.
This study has examined the effect of the cytokine interleukin 1 (IL-1) on metastasis formation by the human melanoma A375M in nude mice. We have found that human recombinant IL-1 beta (a single injection greater than 0.01 micrograms per mouse i.v. given before tumor cells) induced an augmentation of experimental lung metastases from the A375M tumor cells in nude mice. This effect was rapidly induced and reversible within 24 h after IL-1 injection. A similar effect was induced by human recombinant IL-1 alpha and human recombinant tumor necrosis factor, but not by human recombinant interleukin 6. 5-[125I]odo-2'-deoxyuridine-radiolabeled A375M tumor cells injected i.v. remained at a higher level in the lungs of nude mice receiving IL-1 than in control mice. In addition, IL-1 injected 1 h, but not 24 h, after tumor cells enhanced lung colonization as well, thus suggesting an effect of IL-1 on the vascular transit of tumor cells. These findings may explain the observation of enhanced secondary localization of tumor cells at inflammatory sites and suggest that modulation of secondary spread should be carefully considered when assessing the ability of this cytokine to complement cytoreductive therapies.
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
R
R
Giavazzi
A
A
Garofalo
M R
MR
Bani
M
M
Abbate
P
P
Ghezzi
D
D
Boraschi
A
A
Mantovani
E
E
Dejana
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D007065:Idoxuridine / Q000493:pharmacokinetics; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007700:Kinetics; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary*; D008297:Male; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000473:pathology*; D009368:Neoplasm Transplantation; D011865:Radioisotope Dilution Technique; D011994:Recombinant Proteins / Q000494:pharmacology; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D015850:Interleukin-6; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007065:Idoxuridine