In vitro detection of suspected drug in maculopapular drug reaction to antibiotics using secreted cytokines from drug-specific activated T cells

Abstract

Abstract Background Maculopapular drug eruption (MPE) in reaction to antibiotics is associated with enhanced expression of T-helper (Th)1 cytokines such as interferon gamma (IFN-gamma) or Th2 cytokines such as interleukin (IL)-5. Identifying the culprit drug usually involves rechallenge, which may not be forthcoming. Memory lymphocytes remain responsive to the culprit drug long after the reaction has resolved. On reactivation in vitro, there is increased proliferation and expression of certain markers, which provides us with an opportunity to predict the causal drug. Objectives The study aimed to assess drug-specific cytokine production (IL-5 and IFN-gamma) in peripheral blood mononuclear cell (PBMC) culture supernatants to predict the causal antibiotic in cases of MPE. Methods PBMCs of 18 patients who developed MPE to 20 suspected antibiotics (2 patients had 2 suspected antibiotic allergies each), along with 11 drug-matched healthy controls, were incubated for 5 days with the respective drugs at 2 different concentrations. Secreted cytokines were measured in the supernatants, using enzyme-linked immunosorbent assay (ELISA) for IL-5 and IFN-gamma, at 6 h of incubation, then on day 2 and day 5. Results Drug-specific IL-5 and IFN-gamma production could be demonstrated in 65% and 74% of the cases, respectively. Maximal secretion of IL-5 and IFN-gamma was observed on day 5 and day 2 of incubation, respectively. The cut-off delta values, defined as the difference in cytokine concentration between drug-stimulated and unstimulated samples, were 4 pg mL−1 for IL-5 and 6 pg mL−1 for IFN-gamma. Conclusions The measurement of drug-specific secretion of IL-5 and IFN-gamma using ELISA is a valuable method for detecting antibiotic-induced MPE.