Correlation between the capacity to activate macrophages in vitro and the antitumor activity in vivo of lipopolysaccharides from different bacterial species.
The correlation between the activation of macrophages by lipopolysaccharides (LPS) from four different bacterial species and their antitumor effect in a rat model of colon cancer was investigated. The efficacy of LPS from Neisseria meningitidis (Nm), Salmonella minnesota (Sm), Escherichia coli (Ec) and Bordetella pertussis (Bp) was evaluated as the smallest concentration inducing rat peritoneal macrophages (pm psi) to produce tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-6 and nitric oxide (NO). The cytokine production was measured in bioassays and NO production quantitatively with Griess reactant. Nm was the most effective LPS with concentrations of 1 ng/10(6) pm psi for the induction of TNF, IL-1 and IL-6 activities and 0.01 ng/10(6) pm psi for the induction of NO production. The range between efficacy of different LPS was broad from 1 to 10(4)-10(5) for TNF activity, 1 to 10(2)-10(3) for NO production and IL-6 activity and 1 to 10-10(2) for IL-1 activity. In vivo antitumor effect was evaluated on the growth of peritoneal carcinomatosis. Complete tumor regressions were observed, the LPS rating with respect to decreasing efficacy was Nm, Sm, Ec then Bp; Nm, Sm and Ec were very closed while Bp was not effective. These results show the correlation between the antitumor effect in vivo of LPS and their capacity to induce in vitro IL-1 activity, but not between their ability to induce NO production, TNF and IL-6 activities.
Blondiau
C
C
Unit 252 INSERM, Faculté de médecine, Dijon, France.
Lagadec
P
P
Lejeune
P
P
Onier
N
N
Cavaillon
J M
JM
Jeannin
J F
JF
D000818:Animals; D001419:Bacteria / Q000737:chemistry*; D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000628:therapy*; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide