In vitro responses of multiple cytokines to purified protein derivative in healthy and naturally Mycobacterium tuberculosis‐infected rhesus monkeys (Macaca mulatta)

Abstract

Background:As the widely used biomarker of whole-blood stimulation assays for tuberculosis diagnosis, the release of IFN-γ might be affected by multiple factors, such as immunosuppression and some infectious agents. Here, we evaluated additional cytokines as diagnostic biomarkers.Methods: Forty-three cytokines were measured by Luminex xMAP technologies in 30 healthy and 10 naturally Mycobacterium tuberculosis (MTB)-infected rhesus monkeys pre-and post-stimulation by purified protein derivative (PPD). Results:After stimulation, production of 23 and 38 cytokines was markedly increased in healthy and MTB-infected macaques, respectively. A comparison of the stimulation index (SI) between MTB infections and healthy macaques showed that the SIs of 32 cytokines in MTB-infected macaques were significantly higher than those in healthy macaques. Pooling the results, eight cytokines were suggested as ideal biomarkers for a whole-blood stimulation assay for MTB diagnosis. Conclusion: PPD could induce multiple cytokine responses in either healthy or MTBinfected monkeys, and eight cytokines had reliable predictive capacity as diagnostic biomarkers of MTB infection. K E Y W O R D S M tuberculosis, multiple cytokine responses, nonhuman primates, whole-blood stimulation assay