Enhancement of anti-OVA IgG2c production in vivo by enalapril

Abstract

Angiotensin-converting enzyme (ACE) inhibitors have non-hemodynamic, pleiotropic effects on the immune response. The effects of ACE inhibitors on the production of cytokines and T-cell functions are well established. However, little is known on the effects of these medicines on humoral response to foreign antigens. In this study, we investigated the effect of enalapril treatment on ovalbumin (OVA)-specific IgG1 and IgG2c production in mice determined by ELISA. Two groups of 8-week-old C57BL/6 females mice (3–4/group) were subcutaneously immunized with OVA (10 μg/animal) in presence of Alhydrogel (1 mg/mouse) and boosted at day 21. The mice were treated with enalapril (5 mg/kg daily, po) or were left without treatment for one month. The animals were bled from the orbital plexus on days 0, 7, 14, 21, and 28 after the first immunization and the sera were stored at –20°C until usage. OVA-specific serum IgG1 and IgG2c were determined by ELISA using serum from each individual animal. The results showed that enalapril significantly increased anti-OVA serum IgG2c in the secondary response without affecting IgG1 synthesis. These data expand our understanding on the properties of enalapril on the immune response, including antibody production.

Immunomodulatory Activity of the Most Commonly Used Antihypertensive Drugs—Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers

“…In an experimental model of infection with dengue virus, enalapril administration seemed to normalize the levels of IL-1beta and decreased the number of cells expressing viral antigen [58]. In diabetic nephropathy this medicament failed to modulate the B cell-mediated immune response [59], which is contradictory to the previously mentioned impact of enalapril on humoral immunity in healthy mice [55]. On the other hand, treatment with this drug may promote macrophage polarization towards the M1 phenotype [59].…”

“…This drug impacts the humoral immunity as well. It has been shown that enalapril administration significantly increases the production of IgG2c without affecting IgG1 synthesis in mice immunized with ovalbumin [55]. However, enalapril-induced effects seem to depend on mouse sex, and thus likely on the activity of sex hormones, since this drug causes the reduction of production of pro-inflammatory IL-1α, protein-1 monocyte chemoattractant, and macrophage-1a protein in females, and increases the synthesis of anti-inflammatory cytokine IL-10 in males [56].…”

“…-IL-2 and IL-10 synthesis, which correlates with an increase in the number of CD4+CD103+CD25spleen-resident T cells [35]; -the number of circulating endothelial progenitor cells after ischemic stress [54]; -the production of IgG2c without affecting IgG1 synthesis in mice immunized with ovalbumin [55]; -the synthesis of anti-inflammatory cytokine IL-10 in males mice [56].…”

Exploring the Impact of ACE Inhibition in Immunity and Disease

“…Research relating to ACE inhibition and immune impact is limited to cytokine production, adaptive immunity, and autoimmune diseases with conflicting evidence across multiple studies regarding immune advantage or disadvantage [ 78 ]. ACE and Ang II have increasing roles in mediating inflammation and altering immune cell populations as presented above.…”

“…Enalapril resulted in an increase in CD4 + T lymphocyte maturation and IL-10 production, with macrophage polarization shifted toward the M1 state. IgG1 production was unaffected by enalapril treatment; however, IgG2c levels were increased after 4 weeks in lupus-prone mice [ 78 ]. Whether these changes are Ang II-dependent or Ang II-independent is unknown and should be investigated further in the future by treating with ARBs in parallel.…”