T. Kambayashi et al., POTENTIAL INVOLVEMENT OF IL-10 IN SUPPRESSING TUMOR-ASSOCIATED MACROPHAGES - COLON-26-DERIVED PROSTAGLANDIN E(2) INHIBITS TNF-ALPHA RELEASEVIA A MECHANISM INVOLVING IL-10, The Journal of immunology, 154(7), 1995, pp. 3383-3390
The administration of murine TNF-alpha to colon (C)-26 bearing mice, s
ignificantly protects the host against the catabolic effects of the tu
mor. This effect of exogenous TNF-alpha can be primarily attributed to
tumor lysis rather than to a direct anticachectic action. Murine peri
toneal macrophages cultured with the C-26 line or with C-26 culture su
pernatant do not release TNF-alpha in response to LPS stimulation. The
reduction in TNF-alpha levels is associated with a significant increa
se in IL-10 levels. Single cell suspension of freshly disaggregated C-
26 tumor (which contains host macrophages), do not produce TNF-alpha b
ut contain significant levels of PGE(2) and IL-10. In contrast, PGE(2)
but not TNF-alpha or IL-70 can be detected in the C-26.IVX cell line
that is used to generate tumors in vivo. Neutralizing anti IL-10 Ab bu
t not isotype-matched Ab, significantly reverses the inhibitory effect
of the tumor cells and their culture supernatant on macrophage TNF-al
pha release. Additional evidence is presented to indicate that the C-2
6-derived inhibitory activity is related to PGE(2). Taken together, th
ese results support the hypothesis that tumor-derived PGE(2) prevents
tumor-infiltrating macrophages from producing TNF-alpha, in part by au
gmenting macrophage IL-10 synthesis.