A Limulus antilipopolysaccharide factor-derived peptide exhibits a new immunological activity with potential applicability in infectious diseases

Previous studies have shown that cyclic peptides corresponding to residues 35 to 52 of the Limulus antilipopolysaccharide (anti-LPS) factor (LALF) bin d and neutralize LPS-mediated in vitro and in vivo activities. Therapeutic approaches based on agents which bind and neutralize LPS activities are par ticularly attractive because these substances directly block the primary st imulus for the entire proinflammatory cytokine cascade. Here we describe ne w activities of the LALF(31-52) peptide, other than its LPS binding ability . Surprisingly, supernatants from human mononuclear cells stimulated with t he LALF peptide are able to induce in vitro antiviral effects on the Hep-2 cell line mediated by gamma interferon (IFN-gamma) and IFN-alpha. Analysis of the effect of LALF(31-52) on tumor necrosis factor (TNF) and nitric oxid e (NO) production by LPS-stimulated peritoneal macrophages revealed that a pretreatment with the peptide decreased LPS-induced TNF production but did not affect NO generation. This indicates that the LALF peptide modifies the LPS-induced response. In a model in mice with peritoneal fulminating sepsi s, LALF(31-52) protected the mice when administered prophylactically, and t his effect is related to reduced systemic TNF-alpha levels. This study demo nstrates, for the first time, the anti-inflammatory properties of the LALF- derived peptide. These properties widen the spectrum of the therapeutic pot ential for this LALF-derived peptide and the molecules derived from it. The se agents may be useful in the prophylaxis and therapy of viral and bacteri al infectious diseases, as well as for septic shock.