Multiformic modulation of endotoxin effects by linomide.
Linomide is a potent immunomodulator that either enhances or suppresses certain immunological processes. Of particular interest is this compound's capacity to inhibit a variety of organ-specific autoimmune diseases. Here, we report on the effects of linomide on several immunological reactions elicited by endotoxin (LPS), both in vivo and in vitro. In rats and mice linomide inhibited the elicitation of endotoxin-induced uveitis (EIU), an acute inflammatory eye disease that develops within 24 h following footpad injection of LPS. Linomide also inhibited the production of TNF-alpha and IL-6 by LPS-stimulated rat and mouse macrophage monolayers. On the other hand, treatment with linomide significantly increased the levels of IL-1beta (mice and less in rats), IL-6 (rats), and TNF-alpha (mice) in serum samples collected 2 h following injection with LPS. The increased production of proinflammatory cytokines in linomide-treated mice was also indicated by the enhanced lethal effect of LPS in these mice. The finding of elevated levels of these cytokines in animals with suppressed EIU is also in line with previous observations of an inverse relationship between EIU severity and levels of TNF-alpha. Data recorded here underscore the unique capacity of linomide to both enhance and suppress the immune system.
Shalev
M
M
The National Eye Institute, NIH, Bethesda, Maryland 20892, USA.
Ko
A
A
Gelderman
M P
MP
Fortin
E
E
Reed
G
G
Slavin
S
S
Gery
I
I
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D001082:Aqueous Humor / Q000737:chemistry; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins; D005260:Female; D006912:Hydroxyquinolines / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control
D000276:Adjuvants, Immunologic; D004731:Endotoxins; D006912:Hydroxyquinolines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C045282:roquinimex