A B S T R A C T This report examined the effect of corticosteroids in vitro on human peripheral blood monocytes, essential cells in both immune and nonimmune cellular defense mechanisms. Monocyte chemotaxis in response to sera, Escherichia coli filtrate, and lymphokine chemotactic factor was markedly reduced (P < 0.01) by hydrocortisone succinate (HCS) at 16 Ag/ml. Methylprednisolone succinate and unesterified hydrocortisone produced similar impairment of monocyte chemotaxis while two drugs which unmodified do not enter cells, hydrocortisone phosphate (HCP) and cortisone acetate, had no effect on chemotaxis. HCS also significantly impaired monocyte random migration at 16 jug/ml. Monocyte bactericidal activity was reduced by HCS at 16 Ag/ml (P < 0.01) ) but was not affected by HCP even at 120 Lg/ml. In comparison, HCS did not alter granulocyte chemotaxis even at 500 Ag/ml, and bactericidal activity was reduced at 16 jg/ml (P < 0.01). Monocyte phagocytosis of cryptococci was reduced only 20% (P < 0.05) at 120 Ag/ml. HCS at 120 Ag/ml did not alter monocyte base-line or postphagocytic hexosemonophosphate shunt activity, viability by trypan blue exclusion, adherence to tissue culture flasks, or surface binding of IgG globulin. These corticosteroid-induced defects in monocyte function may contribute to reduced cellular defense during corticosteroid therapy.

Since high-dose corticosteroid therapy appears to impair cellular defense mechanisms, this study examined its effect on human monocyte function. Fifteen normal volunteers were studied before and after a three-day course of prednisone therapy (50 mg every 12 hours for six doses). A transient period of monocytopenia occurred during the first few hours of therapy. Monocyte killing of Staphylococcus aureus was reduced in nine subjects from 5.6 plus or minus 0.2 (plus or minus S.E.) X 10-6 organisms before to 1.3 plus or minus 0.4 x 10-6 organisms at completion of therapy (p less than 0.01). Similary, killing of Candida tropicalis four subjects fell from 9.3 plus or minus 0.6 to 0.6 plus or minus 0.3 x 10-6 organisma (p less than 0.01). Bactericidal activity returned to normal levels 48 hours after the last dose of prednisone. These same monocyte preparations had normal or increased chemotactic response, phagocytic rate of cryptococci, hexosemonophosphate-shunt response to phagocytosis and ultrastructural characteristics. This impairment of bactericidal and fungicidal activity during prednisone therapy may contribute to the infectious complications seen in patients receiving comparable doses of corticosteroids.

A B S T R A C T Recent studies indicate that oxygen radicals such as superoxide or singlet oxygen may be important in the functional activity of human granulocytes. We have examined the possible importance of these radicals in the functional capacity of human blood monocytes. Monocytes, like granulocytes, generate chemiluminescence during phagocytosis. Chemiluminescence is impaired 50-90% by superoxide dismutase, an enzyme which enhances the dismutation of superoxide to hydrogen peroxide. These results indicate that superoxide is related to the chemiluminescence generated by monocytes. Superoxide dismutase in a concentration which impaired chemiluminescence also impaired the staphylococcal killing by monocytes. Hexose monophosphate shunt activity and hydrogen peroxide production by granulocytes and monocytes were also evaluated. The oxidation of [1-14C]glucose was used as a measure of hexose monophosphate shunt activity and the oxidation of ["4C]formate as an estimation of hydrogen peroxide production. The oxidation of both substrates by monocytes was increased during phagocytosis but, in contrast to results in granulocytes, was not further increased by the addition of superoxide dismutase.These data indicate that superoxide may be important in bactericidal activity of human monocytes. Our results also suggest that the metabolism of oxygen radicals in monocytes and granulocytes may be different.

No abstract

The purpose of this study was to determine if chronic exposure to low levels of carbon monoxide (CO) in man results in tissue hypoxia. For this reason, nine smokers (more than one pack of cigarettes per day) were studied. The presence of hypoxia was assessed by measurement of red cell mass (RCM). The effect of CO on intraerythrocytic factors involved with oxygen delivery was determined by measurement of oxygen-hemoglobin affinity (P50) and of red cell 2,3-diphosphoglycerate (DPG) and adenosine triphosphate (ATP). Values were compared to those of 18 nonsmokers of similar age, sex, and race. Values for carboxyhemoglobin (COHb), RCM, hemoglobin, hematocrit, and red cell count were significantly higher in the smokers. DPG levels were unaltered, while P50 and ATP levels were significantly lower in smokers. These data suggest that chronic exposure to low levels of CO results in tissue hypoxia, probably as a result of decreased blood oxygen carrying capacity and increased blood-O2 affinity. Adaption is reflected in an increased RCM and not by intraerythrocytic changes. The response in RCM may be to levels seen in polycythemia vera, as evidenced by a value of 37.6 in one smoker whose RCM fell to normal after discontinuing cigarettes. This study indicates that smoking causes mild erythrocytosis comparable to that seen in spurious or stress polycythemia. It also suggests that chronic exposure to low levels of CO may further embarrass tissue oxygen supply in patients with anemia, heart disease, chronic lung disease, and cerebral vascular disease in whom oxygen delivery to tissues is already marginal.