Morphine depresses macrophage numbers and function in mouse spleens.

Abstract

Our laboratory has previously observed that mice implanted with slow-release morphine pellets exhibit profound suppression of their capacity to mount an in vitro antibody response to sheep red blood cells (SRBC) (Bussiere et al., 1992a, b). Suppression was blocked by simultaneous implantation of a naltrexone-releasing pellet, showing that the diminished plaque-forming cell (PFC) responses were mediated via a classical opioid pathway. Although in vitro antibody formation to SRBCs requires the interaction of macrophages, T-cells and B-cells (Fig. 1), macrophages appear to be central to the immu- nosuppressive effect of morphine. Addition of normal splenic macrophages, but not lymphocyte-enriched nonadherent splenocytes, to spleen cell cultures from morphine-pelleted mice restored in vitro antibody production (Bussiere et al., 1993). Further, IL-1, IL-6 and IFN-γ, but not IL-2, IL-4 or IL-5 restored antibody responses of opioid-suppressed cultures (Bussiere et al., 1993). The observation that suppression is reversed by cytokines which are produced by macrophages or which activate macrophages suggests that deficient macrophage function is an important factor in the morphine-induced immunosup- pression. Other evidence that morphine impairs macrophage function in mice includes the decreased ability of colony-stimulating factor-treated bone marrow cells to differentiate into macrophage colonies following morphine treatment in vivo or in vitro (Roy et al., 1991) and the decreased phagocytic capacity (Rojavin et al., 1993; Szabo et al., 1993) of murine peritoneal macrophages presented with the yeast Candida albicans following exposure to morphine or other opioids.