HYPERSTIMULATION OF LEUKOCYTES BY PLASMA FROM CARDIOPULMONARY BYPASS PATIENTS IS DIMINISHED BY ALPHA-MSH PRETREATMENT

Cardiopulmonary bypass (CPB) results in a diffuse inflammatory respons e characterized in part by hyperstimulation of leukocytes. We have pre viously shown that this hyperstimulation appears to be due, in part, t o an increase in the release of biological response modifiers (BRMs) s uch as cytokines. In the present study, we evaluated the ability of a naturally occurring immunocyte inhibitory substance, alpha-melanocyte- stimulating hormone (alpha-MSH), to prevent the hyperstimulation cause d by CPB. Monocytes and granulocytes were pretreated with alpha-MSH (1 0(-6) M) before exposing the cells to plasma obtained from patients wh o had undergone CPB, as CPB plasma would stimulate naive monocytes and granulocytes in a manner similar to that observed in CPB patients. Pr etreatment of these cells with a-MSH significantly diminished the hype rstimulation 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 alpha-MSH, alpha-MSH had no effect, Furthermore , use of the specific neutral endopeptidase inhibitor, phosphoramidon, significantly increased the efficacy of alpha-MSH in inhibiting CPB-i nduced immunocyte activation. The data demonstrate that pretreatment o f monocyte/macrophages and granulocytes with alpha-MSH effectively inh ibits the immune hyperstimulation induced by CPB-plasma exposure. In a ddition, the data strongly suggest that preexposure to other naturally occurring immune inhibitory substances may diminish the hyperstimulat ion associated with CPB. The study also further confirms that this hyp erstimulation may, in part, be due to BRMs released from immunocytes.