Chest
Volume 111, Issue 3, March 1997, Pages 698-705
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Laboratory and Animal Investigations
Acute Activation of Circulating Polymorphonuclear Neutrophils Following In Vivo Administration of Cocaine: A Potential Etiology for Pulmonary Injury

https://doi.org/10.1378/chest.111.3.698Get rights and content

Crack cocaine has become a major drug of abuse in the United States and its use is associated with a broad spectrum of pulmonary complications. 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 lung 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 IV placebo (saline solution). Samples of blood were obtained from a peripheral venous catheter and blood cells were isolated before and 10 to 45 min after treatment. The administration of either cocaine base or cocaine HCl, but not their corresponding placebos, resulted in the activation of circulating polymorphonuclear neutrophils (PMNs). Exposure to cocaine 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, also 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 associated with both acute and chronic lung injury. These studies demonstrate that short-term in vivo exposure to cocaine activates the effector function and cytokine production of circulating PMNs. Therefore, it is possible that bursts of acute inflammatory activity resulting from crack use could contribute to lung injury.

Section snippets

Subjects

Twenty-four current crack-smoking subjects, including 17 men and 7 women, were recruited from a cohort of crack smokers participating in ongoing studies9,12 of the pulmonary effects of habitual use of cocaine, as well as from chemical dependency treatment programs in the local community. All subjects were between the ages of 21 and 50 years, and were regular smokers of alkaloidal cocaine, with only limited use of IV cocaine (≤12 times per lifetime). Exclusionary criteria, described in detail

Subject Characteristics

Demographic and smoking characteristics of the 24 study subjects are shown in Table 1. Subjects were in their fourth to fifth decade of life, and reported current smoking of at least 0.2 g (mean=1.3 g) of crack cocaine per week, with a duration of smoking of at least 3 years. Approximately two thirds of the subjects also currently smoked tobacco and/or marijuana.

Functional Analysis of Effector Cells

PMNs were assayed for their ability to kill S aureus before and after administration of cocaine or placebo. As shown in Figure 1, the

DISCUSSION

The mechanisms by which crack cocaine injures the lung are not well defined. However, the frequent autopsy findings of diffuse alveolar damage, interstitial pneumonitis, and pulmonary fibrosis in crack users suggest that both acute and chronic inflammatory reactions are involved.6, 7, 8 The present study was designed to assess the effects of short-term cocaine exposure on circulating inflammatory cells. Our findings suggest that short-term exposure to cocaine, either by inhalation or the IV

ACKNOWLEDGMENTS

The authors thank Michael Simmons for statistical analysis and figure preparation, and Wendy Aft for preparation of the manuscript.

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