Anti-Tuberculosis Drugs and Human Polymorphonuclear Leukocyte Functions

Background: The polymorphonuclear leukocyte (PMN) is considered to be of importance in the early stages of human tuberculosis (TB). We examined the four drugs (rifampicin, isoniazid, pyrazinamide and ethambutol) commonly used in the DOTS (directly observed treatment, short-course) strategy against TB for their effects on the functions of the human PMN, separately and combined. Methods: PMNs were incubated with subtherapeutic, therapeutic and supratherapeutic concentrations of the drugs before being tested for phagocytosis and oxidative burst capacity with Staphylococcus aureus opsonized with pooled human serum as stimuli. Flow cytometric techniques were used to compare PMN phagocytosis and oxidative burst with and without incubation in different concentrations of the drugs. Results: None of the drugs influenced PMN phagocytosis as measured by flow cytometry. Oxidative burst was attenuated only with the highest (and supratherapeutic) concentrations of isoniazid and of the combined drugs as compared to lower concentrations. Conclusions: This suggests that any deterioration in PMN function observed in TB is probably associated with the disease per se and not with the anti-TB treatment. Copyright (C) 2011 S. Karger AG, Basel