Abstract:
Even after attainment of sustained viral suppression following implementation of highly
active antiretroviral therapy, HIV-infected persons continue to experience persistent,
low-grade, systemic inflammation. Among other mechanisms, this appears to result
from ongoing microbial translocation from a damaged gastrointestinal tract. This HIVrelated
chronic inflammatory response is paralleled by counteracting, but only partially
effective, biological anti-inflammatory processes. Paradoxically, however, this antiinflammatory
response not only exacerbates immunosuppression but also predisposes
for development of non-AIDS-related, non-communicable disorders. With respect to
the pathogenesis of both sustained immunosuppression and the increased frequency
of non-AIDS-related disorders, the anti-inflammatory/profibrotic cytokine, transforming
growth factor-β1 (TGF-β1), which remains persistently elevated in both untreated and
virally suppressed HIV-infected persons, may provide a common link. In this context, the
current review is focused on two different, albeit related, harmful activities of TGF-β1 in
HIV infection. First, on the spectrum of anti-inflammatory/immunosuppressive activities
of TGF-β1 and the involvement of this cytokine, derived predominantly from T regulatory
cells, in driving disease progression in HIV-infected persons via both non-fibrotic and
profibrotic mechanisms. Second, the possible involvement of sustained elevations in
circulating and tissue TGF-β1 in the pathogenesis of non-AIDS-defining cardiovascular,
hepatic, pulmonary and renal disorders, together with a brief comment on potential
TGF-β1-targeted therapeutic strategies.
