Interleukin-1 alpha reduces the severity of the vascular leak syndrome produced by interleukin-2 and interleukin-2 plus interferon-alpha.
Histological and ultrastructural changes were investigated in lung, liver, and heart of mice given interleukin-2 (IL-2), either alone or in combination with other cytokines. IL-2 induced a vascular leak syndrome (VLS) of a moderate degree with infiltration of lymphoid cells, moderate endothelial damage, mild hepatic parenchymal damage, and minimal myocardial alterations. Interferon-alpha (IFN-alpha) produced infiltration mainly of monocytes/macrophages in liver and heart; endothelial cell damage was absent in lung and heart and minimal in liver. Interleukin-1 alpha (IL-1 alpha) caused an increased number of neutrophils in liver and lung; VLS and parenchymal cell and endothelial damage were not found. The VLS and the cellular damage caused by the combination of IL-2 and IFN were much more severe than those produced by IL-2 alone. In animals treated with IL-2, IFN-alpha, and IL-1 alpha, VLS was minimal and parenchymal and endothelial cell damage were less severe than after IL-2 alone or IL-2 plus IFN-alpha. Taken together, these observations show that IL-1 alpha reduces ultrastructural changes produced by IL-2 and IFN-alpha. This reduction may be clinically useful in the treatment of neoplasms.
Fujita
S
S
Pathology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Maryland 20892.
Puri
R
R
Yu
Z X
ZX
Travis
W
W
Yamaguchi
M
M
Ferrans
V J
VJ
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004487:Edema / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D016898:Interferon-alpha / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology; D013577:Syndrome
D016898:Interferon-alpha; D007375:Interleukin-1; D007376:Interleukin-2