Multiformic modulation of endotoxin effects by linomide

Linomide is a potent immunomodulator that either enhances or suppresses cer tain immunological processes. Of particular interest is this compound's cap acity to inhibit a variety of organ-specific autoimmune diseases. Here, we report on the effects of linomide on several immunological reactions elicit ed by endotoxin (LPS), both in vivo and in vitro. In rats and mice linomide inhibited the elicitation of endotoxin-induced uveitis (EIU), an acute inf lammatory eye disease that develops within 24 h following footpad injection of LPS. Linomide also inhibited the production of TNF-alpha and IL-6 by LP S-stimulated rat and mouse macrophage monolayers. On the other hand, treatm ent with linomide significantly increased the levels of IL-1 beta (mice and less in rats), IL-6 (rats), and TNF-LU (mice) in serum samples collected 2 h following injection with LPS. The increased production of proinflammator y cytokines in linomide-treated mice was also indicated by the enhanced let hal effect of LPS in these mice. The finding of elevated levels of these cy tokines in animals with suppressed EIU is also in line with previous observ ations of an inverse relationship between EIU severity and levels of TNF-al pha. Data recorded here underscore the unique capacity of linomide to both enhance and suppress the immune system. (C) 1999 Academic Press.