Effects of cocaine on macrophage functions: Phagocytosis and activation to the cytotoxic state



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Texas Tech University


One of the most "fashionable" as well as dangerous drugs abused in this country is cocaine. Very little is known about the effects of cocaine on the immune system. Since macrophages play a central role in both the cellular and the humoral arms of the immune system, this study focused on the effects of cocaine on murine peritoneal macrophage functions, viz., phagocytosis and activation to the cytotoxic state.

Phagocytosis is one of the most important components of the host defenses against invading microorganisms once the outer epithelial surface of the body has been breached. In the present study, cocaine injected intraperitoneally was found to increase phagocytic activity of isolated macrophages in vitro; but decreased it when measured by an in vivo assay. The respiratory burst, which is usually correlated with phagocytosis, was enhanced by cocaine. Macrophage activation was studied by measuring macrophage- mediated cytotoxicity (MMC), i.e., the acquisition of competence to destroy neoplastic cells in the absence of antibody. Macrophages from cocaine-injected mice demonstrated a reduced capacity for killing neoplastic cells; as well as a reduction in the secretion of reactive nitrogen intermediates. The latter represent a major product used by macrophages to kill cells. Macrophage receptors/ surface proteins involved in phagocytosis and activation were studied using flow cytometry. A number of these surface receptors were dramatically altered by exposure to cocaine. The presumed toxic metabolites of cocaine, benzoylecgonine and norcocaine, were found to have similar effects on macrophage functions.

The present studies clearly demonstrate that cocaine affeas phagocytosis and activation to the cytotoxic state. This translates into impairment of certain non-specific immune responses. These results taken in their entirety suggest that the ability of cocaine to alter macrophage functions could modify specific immune responses resulting in a compromised immune system.