A Study of Elevated Interleukin-8 (CXCL8) Detection of Leukocyte Migration Inhibitory Activity in Patients Allergic to Beta-Lactam Antibiotics

ABSTRACT Background The leukocyte migration test (LMT) is effective in identifying the causative drug in drug allergies. Both leukocyte migration activating activity (LMAA) and leukocyte migration inhibitory activity (LMIA) are involved in the development of drug allergies. However, no cytokines associated with LMIA have been identified to date. Because CXCL8 played an important role in neutrophil infiltration and activation, we performed the LMT and measured CXCL8 levels in patients with hypersensitivity to beta-lactam antibiotics (beta-lactams) and antipyretic analgesics (APAs) and investigated the pathogenic mechanism of hypersensitivity to these drugs. Methods The LMT was performed according to an improved version of the agarose plate method and CXCL8 levels in the reacted solution that had been stored as described were measured using a solid-phase sandwich enzyme-linked immunosorbent assay. Results Migration index (MI) values for the LMT were 77.7 ± 11.7 for patients with hypersensitivity to beta- lactams and 83.6 ± 1.9 for those with hypersensitivity to APAs. The CXCL8 concentrations were significantly higher in patients after beta-lactams administration (175.9 ± 71.2 ng/mL) than those without beta-lactams administration (48.3 ± 34.9 ng/mL). The CXCL8 concentrations were significantly lower in patients after APAs administration (41.7 ± 24.3 ng/mL) than those without APAs administration (63.1 ± 30.2 ng/mL). Conclusions Increased CXCL8 levels produced by beta-lactams administration were accompanied by LMIA. CXCL8 may be involved in LMIA and play a role in beta-lactam allergies. In contrast, the LMIA detected in patients with allergies to APAs may be a cytokine or chemokine other than CXCL8.