Abrogation of macrophage-mediated suppression of T-lymphocyte proliferation with hemoglobin and hemin is a function of iron content.

Hemoglobin, hemin, and ferric ion (Fe) were shown to reverse peritoneal exudate cell (PEC)-mediated suppression of concanavalin A-elicited murine spleen cell activation. Titration of hemoglobin and hemin relative to Fe showed a direct relationship between Fe content and reversal of PEC suppression. Indomethacin enhanced the capacity of all three compounds to abrogate PEC suppression on the order of five- to eight-fold. The capacity of endogenous Fe-containing substances as hemoglobin and its catabolites, e.g., hemin, to modulate macrophage expression may be of special significance at sites of inflammation.