PRODUCTION OF TUMOR-NECROSIS-FACTOR, INTERLEUKIN-6 AND PROSTAGLANDIN-E, BY LPS-STIMULATED RAT BONE-MARROW MACROPHAGES AFTER THERMAL-INJURY - EFFECT OF INDOMETHACIN

The effect of thermal injury on the in vitro production of TNF, IL-6, and PGE(2) by bone marrow-derived, LPS-stimulated rat macrophages was studied. Thermal injury caused a general hyperactivity in the producti on of the mediators by the cells. Indomethacin, a cyclooxygenase inhib itor of PGE(2) synthesis, inhibited the production of IL-6 and PGE(2) but had no effect on the production of TNF. These results suggest that the observed low concentration of PGE(2) produced by the cells was in sufficient to cause inhibition of TNF synthesis; thus, the effect of i ndomethacin would be undetectable. The results also suggest that indom ethacin may act directly in inhibiting the production of IL-6 by the m acrophages. The hyperactive effect of thermal injury on the production of inflammatory mediators by newly differentiated bone marrow derived macrophages can be important in the overall systemic response to the insult.