Which cytokines are known to activate macrophages in chronic inflammatory diseases?

• A. IL-10 and TGF-β
• B. IFN-γ and TNF-α
• C. IL-4 and IL-13
• D. IL-2 and IL-6

Answer: (B)

Macrophage activation in chronic inflammation is driven by signals that push these cells into a classical, proinflammatory state. IFN-γ, produced by Th1 cells and NK cells, binds to its receptor on macrophages and triggers signaling that promotes classical activation (the M1 phenotype). This ramps up microbicidal mechanisms like inducible nitric oxide synthase, boosts reactive oxygen species production, and increases antigen presentation, all of which sustain ongoing inflammation and contribute to granuloma formation in diseases such as tuberculosis and other chronic inflammatory conditions. TNF-α works together with IFN-γ, signaling through its receptors to amplify macrophage activation, enhance phagocytosis, and sustain inflammatory cytokine production, further fueling chronic inflammatory damage.

Other cytokine groups steer macrophages away from this proinflammatory mode. IL-10 and TGF-β dampen activation and promote resolution. IL-4 and IL-13 drive alternative activation (M2), which is more about tissue repair and anti-inflammatory functions rather than the sustained antimicrobial response seen in chronic inflammation. IL-2 mainly supports T-cell growth, and while IL-6 is an inflammatory mediator, it is not the primary driver of macrophage classical activation.

So, IFN-γ and TNF-α best account for activating macrophages in chronic inflammatory diseases.