Figure 1.

Overexpression of IL-6 and its potential negative consequences on the viral immune response. Current scientific evidence supports different scenarios where imbalance on the IL-6 production after viral infection can affect viral clearance, promoting viral persistence and chronic infections. (A) IL-6 might favor Th2 polarization by stimulating STAT3 pathway, and consequently increasing the production of IL-4, and the suppressor of cytokine signaling one protein (SOCS-1). SOCS-1 affects STAT 1 phosphorylation, impairing IFNγ production by decreasing IFNγ self-loop stimulation. (B) IL-6 might impair cytolysis by inducing the production of SOCS-3, affecting phosphorylation of STAT 4, and consequently impairing IFNγ production, an essential IFN type II interferon molecule to promote CD8 and NK cells activation. (C) IL-6 might promote infected cell survival by inducing apoptosis. Overexpression of this cytokine increments Th17 polarization, increasing IL-17 production in the cellular environment. IL-17 pathway induce the production of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma extra-large (Bcl-xL) proteins, which prevent mitochondrion to produce the cytochrome complex protein (Cyt-c) after stimulation by the pro-apoptotic molecule protease Granzyme B, impairing the production of active apoptotic caspase molecules. An additional scenario includes the production of the programmed death ligand 1 protein (PD-L1) by the concerted action of IFN type I and IL-6. Matching between PD-L1 and programed death protein 1 (PD-1) switches off apoptosis mediated by CD8 T cells.