MACROPHAGE-DERIVED TUMOR-NECROSIS-FACTOR AND TUMOR-DERIVED OF LEUKEMIA INHIBITORY FACTOR AND INTERLEUKIN-6 - POSSIBLE CELLULAR MECHANISMS OF CANCER CACHEXIA
Kg. Billingsley et al., MACROPHAGE-DERIVED TUMOR-NECROSIS-FACTOR AND TUMOR-DERIVED OF LEUKEMIA INHIBITORY FACTOR AND INTERLEUKIN-6 - POSSIBLE CELLULAR MECHANISMS OF CANCER CACHEXIA, Annals of surgical oncology, 3(1), 1996, pp. 29-35
Background: The cellular basis for augmented cytokine production in th
e tumor-bearing host is not known. Recently leukemia inhibitory factor
(LIF) and interleukin (IL)-6, produced by a variety of tumors, have b
een implicated as mediators of cachexia. Methods: Five murine tumor ce
ll lines were tested for the production of these cytokines. 4JK tumor
was further tested to determine if IL-1, tumor necrosis factor (TNF),
or cocultivation with RAW 264 cells augmented IL-6 or LIF production.
Results: 4JK from in vivo tumors produced significantly more IL-6 than
did 4JK from culture, indicating that tumor production of IL-6 and LI
F is potentially augmented by infiltrating macrophages. When 4JK was c
ocultured with RAW 264 cells, TNF, or IL-1 in vitro, a three- to 15-fo
ld increase in tumor production of LIF and IL-6 was noted (p(2) less t
han or equal to 0.03). Conversely, in coculture experiments performed
with a neutralizing TNF antibody, a 50% reduction in tumor production
of LIF and IL-6 was noted (p(2) < 0.04). Resting RAW cells produced on
ly minimal quantities of TNF; however, when RAW cells were exposed to
tumor-conditioned supernatant from 4JK, their TNF production was marke
dly increased. Conclusions: In the tumor microenvironment, host macrop
hages may be activated and produce inflammatory cytokines such as TNF.
Local TNF then appears to act on tumor cells to stimulate production
of IL-6 and LIF. Enhanced tumor production of cytokine mediators may c
ontribute to deleterious effects of neoplastic growth on the host.