Effect of ethanol on immune clearance in mice: biphasic alteration of complement-mediated clearance with chronic...

Rate constants (k1 through k4) describing complement-mediated and Fc gamma receptor-mediated components of immune clearance were serially determined in BALB/c mice fed ethanol, 10%, in drinking water, for 24 weeks. A branched series, first order reaction sequence model of immune clearance was used to obtain the rate constants from measurements of the clearance of radiolabeled immunoglobulin G-opsonized, murine erythrocytes. A > 50% decrease in complement-mediated clearance occurred, with a nadir of complement-mediated sequestration (k1) and complement-dependent phagocytosis (k4) at 2 weeks (p < 0.003). Mean k1 and k4 rate constant values returned to control levels by week 6, and k1 increased to elevated values in weeks 10 through 20 (p < 0.05). The rate constant governing C3b deactivation and return of deactivated, sensitized cells back to the circulation (k2) was initially normal but decreased in weeks 6 through 24 (p < 0.05). Neither immunoglobulin G Fc gamma receptor-mediated clearance nor the survival of nonsensitized cells were decreased by ethanol. Mice fed ethanol had a mean blood alcohol level of 14.9 +/- 7.2 mmol/L, and their mean weight and serum complement levels did not differ from untreated controls. Complement-dependent sequestration and phagocytosis did not decrease significantly when rechallenged with 10% ethanol, but the decrease in k2 and increase in k1 did occur on rechallenge. Thus, chronic ethanol ingestion in mice is associated with an initial decrease followed by a small rebound increase in complement-mediated clearance of opsonized cells. Fc gamma receptor-mediated clearance is not decreased, and only the rebound increase in complement-mediated clearance is observed on rechallenge. This model provides a unique opportunity to study selective in vivo effects of ethanol on an important function of the immune system as well as to explore the mechanisms of ethanol tolerance in mice.