ACUTE ACTIVATION OF CIRCULATING POLYMORPHONUCLEAR NEUTROPHILS FOLLOWING IN-VIVO ADMINISTRATION OF COCAINE - A POTENTIAL ETIOLOGY FOR PULMONARY INJURY

Crack cocaine has become a major drug of abuse in the United States an d its use is associated with a broad spectrum of pulmonary complicatio ns. The present study was conducted to determine whether controlled in vivo administration of cocaine (inhaled or IV) alters the function of circulating inflammatory cells in a manner capable of contributing to acute lune; injury. Subjects who regularly smoked crack cocaine were asked to abstain from illicit drug use for at least 8 h, and were then administered one of the following treatments on each of 4 study days: inhaled cocaine base (45 mg), inhaled placebo (4.5 mg cocaine base, a subphysiologic dose), IV cocaine HCl (0.35 to 0.50 mg/kg), or ni plac ebo (saline solution). Samples of blood were obtained from a periphera l venous catheter and blood cells were isolated before and 10 to 45 mi n after treatment. The administration of either cocaine base or cocain e HCl, but not their corresponding placebos, resulted in the activatio n of circulating polymorphonuclear neutrophils (PMNs). Exposure to coc aine in vivo enhanced the antibacterial activity of PMNs, as measured by their ability to kill Staphylococcus aureus. Antitumor activity, as measured in an antibody-dependent cell-mediated cytotoxicity assay, a lso increased following short-term administration of cocaine. Finally, short-term exposure to cocaine enhanced production of interleukin 8, a potent PMN chemoattractant and neutrophil-activating factor associat ed with both acute and chronic lung injury. These studies demonstrate that short-term in vivo exposure to cocaine activates the effector fun ction and cytokine production of circulating PMNs. Therefore, it is po ssible that bursts of acute inflammatory activity resulting from crack use could contribute to lung injury.