Morphine Accelerates the Progression of Sepsis in an Experimental Sepsis Model

Abstract

The idea that exogenous opiates can affect immune function is not entirely new. Historically as early as 1889 the effect of opium on leukocyte phagocytosis was described in a guinea pig model (1). More recently, evidence supporting the role of opiates in suppressing a variety of immunological end points in opiate addicts was reported by Louria et al. (2). The opioid induced modulation of immune function has been implicated in reduced host resistance against invading pathogens. Several key functions such as: lymphocyte prolifera- tive response to mitogens (3), T cell rosette formation (4) and the total number of circulating lymphocytes (5) have all been shown to be reduced in heroin addicts. In animal models morphine treatment has been found to increase mortality rates in experimentally infected mice (6, 7). Similarly, in animal models, lymphocyte proliferative responses (8), NK cell ytotoxicity activity (9, 10) antibody and serum hemolysin formation (11) and the phago- cytic and killing properties of peripheral blood mononuclear leukocytes (6) are all attenu- ated after in vivo chronic morphine exposure. While the mechanisms responsible for morphine induced changes in the immune system are not completely understood, they may be directly mediated through opiate receptors present on lymphocytes (12, 13), indirectly through opiate receptors present in the central nervous system, or by activating the hypotha- lamic—pituitary—adrenal axis (14) to release immunosuppressive glucocorticoids (15).