Ibrutinib May Inhibit Macrophage Response to Tuberculosis

Ibrutinib may inhibit the macrophage-mediate response to Mycobacterium tuberculosis (Mtb) among patients with chronic lymphocytic leukemia (CLL), according to an abstract presented at the XVII International Workshop on Chronic Lymphocytic Leukemia (iwCLL).¹

Ibrutinib is a Bruton’s kinase inhibitor used for the treatment of CLL, a B cell disease, including in regions of the world with high incidence of Mtb. It also has effects on other immune cells including T cells, NK cells, and macrophages. This study evaluated the effect of ibrutinib on macrophage polarization and the effector response against Mtb.

Macrophages were collected from patients with or without CLL. M1 and M2 polarization was induced with GM-CSF plus interferon (IFN)-ɣ and interleukin (IL)-4 or IL-10, respectively. The macrophages were incubated with ibrutinib or the vehicle control during the last 2 days and then analyzed by flow cytometry for cell markers.

M1 polarization — differentiation to a pathogen-fighting profile — was inhibited by ibrutinib by downregulation of CD86 and upregulation of MR, CD16, and CD14. M2 polarization — differentiation to a profile associated with T cell activity and parasitic response — was not affected. Ibrutinib did not affect HLA-DR, CD163, or MerTK expression. Macrophage migration was increased with ibrutinib treatment, which is a characteristic of the M2 profile.

Ibrutinib significantly decreased TNF-α, IL-8, and IL-10 secretion by macrophages from healthy subjects or patients with CLL. The reduction of TNF-α was observed at very low ibrutinib concentrations, whereas IL-8 and IL-10 was affected beginning with 3 μM.

Ibrutinib did not affect Mtb phagocytosis, but slightly increased macrophage bacillary loads at day 3 and 6 post-infection.

The authors stated that these data suggest that the “macrophage-mediated response to Mtb may be compromised in ibrutinib-treated patients. Therefore, an increased awareness should be taken in ibrutinib-treated patients, especially from countries with high incidence rates of tuberculosis.”

Reference

1. Almejún MB, Borge M, Colado A, et al. Effects of ibrutinib on macrophage-polarization and on the immune-response against Mycobacterium tuberculosis. Paper presented at: XVII International Workshop on Chronic Lymphocytic Leukemia; May 12-15, 2017; New York, NY.