Inhibition of lipopolysaccharide-associated endotoxin activities in vitro and in vivo by the human anti-lipid A monoclonal antibody SdJ5-1.17.15

Abstract

The present study evaluated the effect of a novel anti-lipid A monoclonal antibody, termed SdJ5, on the in vitro production of tumor necrosis factor alpha (TNF-a) and interleukin-1f% by endotoxinor lipopolysaccharide (LPS)-challenged human peripheral blood mononuclear cells (hPBMC). In addition, the present study determined whether SdJ5 could neutralize the in vivo toxicity of LPS. SdJ5, at a concentration equal to or greater than 3 iLg/ml, specifically inhibited TNF-a and interleukin-lj production by hPBMC stimulated with every type of LPS and lipid A assessed. SdJ5 also showed a significantly greater inhibition of cytokine production than a nonrelevant human immunoglobulin M myeloma control. The SdJ5-mediated inhibition of TNF-a production was rapid, as the simultaneous addition of the SdJ5 and LPS still resulted in a marked decrease in hPBMC cytokine synthesis. The ability of SdJ5 to neutralize in vivo toxicity was also determined by using LPS from four different strains of gram-negative bacteria. LPS, when preincubated with SdJ5, resulted in a significant decrease in the 24-h mortality rate compared with that for the control. These studies show that the anti-lipid A monoclonal antibody SdJ5 can modulate LPS-induced cytokine production in vitro and increase the survival rate of rats challenged with lethal doses of LPS.

A monoclonal antibody that recognizes phosphatidylinositol inhibits induction of tumor necrosis factor alpha by different strains of Plasmodium falciparum

“…Gram-negative bacteria contain lipopolysaccharide (LPS), which is a powerful stimulant of TNF production. A MAb that binds to lipid A, the biologically active component of LPS, has been shown to inhibit TNF production by LPS derived from different bacteria in vitro (10) and to protect mice challenged with gram-negative bacteria (18).…”

Immunoreactivity and bioactivity of lipopolysaccharide-binding protein in normal and heat-inactivated sera

“…However, heat treatment of sera at 56 or 60ЊC for 30 min (to inactivate the complement system) is a common practice. In a number of recent studies, the effects of LPS on macrophages have been investigated in the presence of heat-inactivated sera (2,3,7,8,13,22), but information on the effect of heat treatment on the LPS-potentiating ability of serum and LBP, is lacking. This study was undertaken to determine the LPS-potentiating activity and LBP content of normal human serum (NHS) and fetal bovine serum (FBS), and their heat sensitivity, using human recombinant LBP (rLBP) as a reference standard.…”