*2.3. IFN-*γ *and IL-2 as Adjunct Therapy*

Production of anti-microbial peptides and other antimicrobial activities exerted by macrophages are stimulated by a panel of cytokines that include TNF (Tumor Necrosis Factor), IFN-γ and interleukin 1 (IL-1). While IFN-γ plays its major role in promoting autophagy and phagosome maturation, TNF increases IFN-γ responsiveness and IL-1 counteracts the detrimental effects of Type I IFN in TB [63]. HDT against TB infection includes IFN-γ and modulators of TNF, which will be discussed later in this review. Concerning IFN-γ, it was demonstrated that its administration to TB patients via the aerosol route is well-tolerated and reduces time to sputum conversion while improving lung repair after the disease [64–66]. However, the role of IFN-γ in controlling TB is still under debate, as reported in a study by Sakai and co-workers, who showed that contribution of CD4-T cell derived IFN-γ is limited and, even worse, sometimes detrimental [67]. Another clinical study, where IL-2 was added during the first month of anti-TB treatment resulted in no benefit [68], thus questioning the relevance of adding cytokines to the existing therapy. Possible side effects and treatment costs should also be considered when exploring the administration of cytokines to TB patients.
