EFFECT OF IRON STATUS ON ENDOTOXIN-INDUCED MORTALITY PHAGOCYTOSIS ANDINTERLEUKIN-1-ALPHA AND TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION

The host susceptibility to endotoxin (lipopolysaccharide, LPS), produc tion of interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alp ha (TNF-alpha) or phagocytosis in resident peritoneal macrophages were examined in iron-deficient and iron-loaded mice. Four groups of weanl ing male CD-1 mice were fed diet containing 7, 120, 5000 or 8000 ppm i ron for 7 w. Body weight gain or hematocrit was not affected by iron c onsumption except for a lower weight gain in mice fed the 8000 ppm iro n diet. Iron deficient and loaded diets produced a marked decrease and increase in liver iron concentration, respectively (P < 0.5). When ch allenged with an ip lethal dose of LPS, mortality was enhanced in iron -deficient and loaded mice (P = 0.035). The production of TNF-alpha an d IL-1 alpha was assessed in the peritoneal macrophages stimulated by LPS in vitro. The production of Il-1 alpha and TNF-alpha was not alter ed in macrophages from iron deficient mice. In contrast, macrophages f rom the 2 iron-loaded groups of mice produced more TNF-alpha (150% of control) without altering IL-1 alpha production. However, the total pe ritoneal leukocyte cell yield was not different among the treatment gr oups. Phagocytosis in the peritoneal macrophages determined by in vitr o uptake of yeast cells was lower in the iron-deficient or loaded mice . This study indicates that iron deficiency and overload enhance LPS t oxicity and impair phagocytosis, whereas excess iron also increases TN F-alpha production by macrophages.