Hyperstimulation of leukocytes by plasma from cardiopulmonary bypass patients is diminished by α-MSH pretreatment

Cardiopulmonary bypass (CPB) results in a diffuse inflammatory response characterized in part by hyperstimulation of leukocytes. We have previously shown that this hyperstimulation appears to be due, in part, to an increase in the release of biological response modifiers (BRMs) such as cytokines. In the present study, we evaluated the ability of a naturally occurring immunocyte inhibitory substance, α-melanocyte-stimulating hormone (α-MSH), to prevent the hyperstimulation caused by CPB. Monocytes and granulocytes were pretreated with α-MSH (10−6 M) before exposing the cells to plasma obtained from patients who had undergone CPB, as CPB plasma would stimulate naive monocytes and granulocytes in a manner similar to that observed in CPB patients. Pretreatment of these cells with α-MSH significantly diminished the hyperstimulation induced by CPB plasma in a concentration-dependent manner. In contrast, when the cells were first or simultaneously exposed to CPB plasma and then to α-MSH, α-MSH had no effect. Furthermore, use of the specific neutral endopeptidase inhibitor, phosphoramidon, significantly increased the efficacy of α-MSH in inhibiting CPB-induced immunocyte activation. The data demonstrate that pretreatment of monocyte/macrophages and granulocytes with α-MSH effectively inhibits the immune hyperstimulation induced by CPB-plasma exposure. In addition, the data strongly suggest that pre-exposure to other naturally occurring immune inhibitory substances may diminish the hyperstimulation associated with CPB. The study also further confirms that this hyperstimulation may, in part, be due to BRMs released from immunocytes.