Risk of Tuberculosis Reactivation in Patients with Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Receiving Non-Anti-TNF-Targeted Biologics

Table 1

Immune cells and factors involved in the immunity against tuberculosis. List of some of the biological drugs used in the treatment of rheumatological disorders that inhibit immune paths.

Cytokine	Producing cell type	Role in tuberculosis	Biological drug inhibiting; this path	References
IFN-γ	T lymphocytes, NK	(1) Activates iNOS pathway; (2) Induces the process of acidification and maturation; of phagosomes; (3) Induces autophagy; (4) Inhibits IL-17 production		[22, 23–26, 32]
TNF-α	T lymphocytes, macrophages	(1) Maintain of granuloma integrity; (2) Changes in TNF-α levels have been correlated with; disease susceptibility; (3) Acts synergistically with IFN-γ to stimulate the; production of NO by macrophages; (4) Influences the expression of chemokines	Infliximab, etanercept,; adalimumab, abatacept	[34–38]
IL-12	Macrophages,; dendritic cells	(1) Individuals with mutations in the IL-12/IFN-γ axis; develop disseminated infection caused by BCG or; nontuberculous species of mycobacteria; (2) Important for MTb clearance	Ustekinumab	[27, 42, 43]
IL-23	Macrophages,; dendritic cells	(1) Mice repeatedly exposed to MTb and BCG; developed strong IL-23-induced Th17 cell pathogenic responses	Ustekinumab	[30]
IL-6	T lymphocytes, macrophages	(1) Pro- and anti-inflammatory properties; (2) Involved in the Th17 and Th22 cell differentiation; (3) Early produced during mycobacterial infection; (4) Involved in macrophage and cytotoxic T-cell differentiation; (5) IL-6-deficient mice develops lethal TB	Tocilizumab	[31, 44–46]
IL-17	CD4 T cells	(1) Has protective immunity against hyper-virulent MTb strains; (2) Removal of IL-17-producing cells enhanced recruitment of Th1 cells to the lung; (3) Has pathogenic role of Th17 cells during chronic infection with MTb or BCG in mice	Secukinumab	[28–30]
IL-1β	Macrophages	(1) Decreases MTb replication activating the innate antimicrobial activity; (2) Induces PGE2 synthesis that leads to a decrease of type I IFN response	Anakinra

IFN: interferon; TNF: tumor necrosis factor; IL: interleukin; NK: natural killer; iNOS: inducible nitric oxide synthase; NO: nitric oxide; BCG: Bacillus Calmette-Guérin; MTb: Mycobacterium tuberculosis; Th: T helper; PGE2: Prostaglandin E2.