Abstract
Prednisolone (PSL), a type of corticosteroid used to treat autoimmune diseases, can increase the risk of infection and osteoporosis. Saireito (114), a Kampo medicine, has an immunosuppressive effect; with its use, the dose of steroids can be reduced. However, its mechanism when used with PSL is still unclear. We used peripheral blood mononuclear cells (PBMCs) from healthy adults to examine the effect of 114 and PSL treatment on PBMC proliferation, T-cell subsets, and cytokine production. PBMCs were cotreated with concanavalin A and 300 μM 114 (either Tsumura & Co. (TJ) or Kracie Holdings (KR)) and 0.0001–1.0 μM PSL for 96 h to create the T-cell mitogen. We then measured the PBMC proliferation; ratio of CD4+ T cells, CD8+ T cells, and T-follicular helper (Tfh) cells; and concentration of cytokines (TNF, IFN-γ, IL-6, IL-10, IL-17A, and IL-21). The proliferation of PBMCs was dose dependently suppressed in both the PSL and PSL + 114 groups (p < 0.05). Combination therapy increased the IC50 in the PSL group (0.0947 μM) by 2.02 and 1.64-fold in the PSL + TJ114 and PSL + KR114 groups, respectively. Both the PSL + 114 groups had an increased ratio of CD4+ T cells compared to the PSL group, with no effect on the ratio of CD8+ T and Tfh cells. Furthermore, the PSL + 114 groups showed increased IL-6 and IL-10 compared to the PSL monotherapy group, although the difference was not significant. There was no significant difference in the TNF, IFN-γ, IL-17A, and IL-21 concentrations between the PSL and PSL + 114 groups. The elevated IC50 with 114 cotreatment suggests diminished immunosuppressive action. Moreover, increased cytokine production by Th2 with 114 cotreatment suggests a restoration of T-cell balance in Th1-mediated autoimmune diseases. However, increased IL-6 suggests potential exacerbation of IL-6-mediated diseases, such as rheumatoid arthritis. Therefore, it is necessary to monitor these clinical parameters when using 114 in combination with PSL.
Highlights
Autoimmune diseases are characterized by abnormal immune function that attack a person’s own healthy cells and tissue [1]
Kampo medicine generally has few adverse effects. e increased safety is a major reason over 80% of doctors in Japan use it for routine care in combination with Western medicine [5]. is includes treatment for autoimmune diseases, with reports showing that treatment for Evidence-Based Complementary and Alternative Medicine rheumatoid arthritis (RA) is effective when using immunosuppressants in combination with Kampo medicine [6]
T-follicular helper (Tfh) cells are increased in the peripheral blood of patients with autoimmune diseases, such as RA and systemic lupus erythematosus (SLE), and the ratio of Tfh cells correlates with disease activity, organ damage, and autoantibody valence [17], such as anti-double-stranded DNA and anticyclic citrullinated peptide antibodies (ACPA)
Summary
Autoimmune diseases are characterized by abnormal immune function (overproduction of autoantibodies and immune cells) that attack a person’s own healthy cells and tissue [1]. Is includes treatment for autoimmune diseases, with reports showing that treatment for Evidence-Based Complementary and Alternative Medicine rheumatoid arthritis (RA) is effective when using immunosuppressants (such as corticosteroids) in combination with Kampo medicine [6]. Saireito (denoted 114) is a Kampo medicine that is used in combination with corticosteroids (especially PSL) in the treatment of autoimmune diseases, such as RA, and is reported to have steroid-like immunosuppressive action [7]. Tfh cells are increased in the peripheral blood of patients with autoimmune diseases, such as RA and SLE, and the ratio of Tfh cells correlates with disease activity, organ damage, and autoantibody valence [17], such as anti-double-stranded DNA (dsDNA) and anticyclic citrullinated peptide antibodies (ACPA). We measured the ratio of CD4+ T cells, CD8+ T cells, and Tfh cells in PBMCs and the concentration of cytokines produced by 1, 2, 17, and Tfh subsets
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