Although multiple studies suggest a potential role for
angiotensin II in
inflammation, most were performed either in vitro or in animals with non-
immune-complex-mediated diseases. Extrapolation of these findings to humans, particularly patients with lupus, which involves multiple immunoregulatory pathways, is unclear. In autoimmune-prone MRL/lpr mice,
angiotensin-converting-enzyme (ACE) inhibition improved survival although to a lesser degree than
cyclophosphamide and diminished the glomerular histopathologic damage,
proteinuria, lymphoid
hyperplasia,
dermatitis, and
hypergammaglobulinemia, with a reduction in
TGF-beta1 and beta 2 expression in the kidneys and renal
chemokine mRNA expression. Spleen levels of
IL-4 and
IL-10 were also reduced. Uncontrolled studies in patients with treatment-refractory
lupus nephritis showed a significant reduction in
proteinuria with
ACE-inhibitors and
Angiotensin receptor blockers treatment. The 'masking' effect of
ACE-inhibitors should be taken into consideration, as an exacerbation of
lupus nephritis may be missed when estimated by the magnitude of
proteinuria, which is decreased by these treatments. No single ACE genotype was consistently associated with subsets of SLE patients. In retrospective analyses,
ACE-inhibitor use predicted a favourable outcome in 94 cases of
pauci-immune vasculitis. The attenuating effect of
angiotensin II inhibitors on the progression of
chronic renal disease is well recognized. The data on the role of this intervention in lupus is limited.