CORRELATION BETWEEN THE CAPACITY TO ACTIVATE MACROPHAGES IN-VITRO ANDTHE ANTITUMOR-ACTIVITY IN-VIVO OF LIPOPOLYSACCHARIDES FROM DIFFERENT BACTERIAL SPECIES

The correlation between the activation of macrophages by lipopolysacch arides (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), Es cherichia coli (Ec) and Bordetella pertussis (Bp) was evaluated as the smallest concentration inducing rat peritoneal macrophages (pm Phi) t o produce tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-G and nitric oxide (NO). The cytokine production was measured in bioassays a nd NO production quantitatively with Griess reactant. Nm was the most effective LPS with concentrations of 1 ng/10(6) pm Phi for the inducti on of TNF, IL-1 and IL-6 activities and 0.01 np/10(6) pm Phi for the i nduction 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) fo r 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 ca rcinomatosis. Complete tumor regressions were observed, the LPS rating with respect to decreasing efficacy was Nm, Sm, Ec then Bp; Nm, Sm an d Ec were very closed while Bp was not effective. These results show t he correlation between the antitumor effect in vivo of LPS and their c apacity to induce in vitro IL-1 activity, but not between their abilit y to induce NO production, TNF and IL-6 activities.