The passive transfer of postendotoxin mouse serum could enhance nonspecific resistance to the development of TA3-Ha transplantable ascites tumor in mice. The postendotoxin serum was not directly cytotoxic to TA3-Ha tumor cells in vitro, nor did it contain significant amounts of residual endotoxin, but it was rich in colony-stimulating factors (CSFs). High-titer CSF serum could be induced by endotoxic lipopolysaccharide (LPS). Nonendotoxic, lipid-free, and polysaccharide-rich hydrolytic breakdown product of LPS (called PS) was less potent but still active in CSF induction. There was a correlation between the level of CSF stimulation and the capacity of the sera to transfer tumor resistance (TUR) Those LPS preparations that had the highest CSF-inducing capacity were the most potent in TUR enhancement. Suppression of CSF production by treatment with theophylline or epinephrine, enhancers of cyclic AMP/cyclic GMP ratios, lowered the enhancement of TUR by endotoxic LPS. The infection of serum donor mice with bacillus Calmette-Guerin (BCG) 18 days prior to LPS treatment gave the highest serum CSF levels and the most potent TUR-inducing serum preparation. Even more notable was the finding that the nontoxic PS preparation could replace toxic LPS in the above BCG-LPS system. The serum harvested from BCG-infected mice 2 hr after PS injection was similarly effective in the passive transfer of TUB. Endotoxin has been demonstrated to produce antitumor effects in two systems. Some tumors can undergo hemorrhage and necrosis after injection of endotoxin, as shown by Shear and associates (1-3). The effect of purified and detoxified endotoxins on sarcoma 37 has been investigated in our laboratories (4). Our earlier findings as well as the findings of others indicate that endotoxin does not act directly on the tumor cells in the hemorrhagic necrosis system. We assumed in 1971 that the antitumor effects were mediated by certain humoral factors produced by endotoxin injection (4). We also reported that pretreatment with endotoxin enhances the nonspecific resistance of mice to challenge with the
The immunological mechanism of the primary in vitro antibody responses to sheep erythrocyte antigens involves soluble immunomodulatory factors. These studies have demonstrated that the stimulation of immunocytes with lipopolysaccharide (LPS) induced the release of a helper factor which appeared to be a monokine. This helper factor was released by stimulated adherent splenocyte cultures but not by nonadherent cell populations. The P388D-transformed macrophage cell line also produced the factor in response to LPS. LPS-induced helper factors were absorbed from solution by bone marrow cells but not by thymocytes, thereby indicating that the factor may selectively bind to B-cells or to undifferentiated stem cells. Mature T-cells did not appear to be involved in the immunostimulatory effects of this macrophage-derived factor as evidenced by the results of several studies. These included observations that splenocytes from athymic BALB/c nu nu mice both produced the factor and responded to it.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.