Abstract
Adalimumab (ADA), a fully human monoclonal tumor necrosis factor (TNF)-α antibody, is one of the most widely used biologics in the treatment of inflammatory diseases. However, ADA can exacerbate infectious conditions, induce paradoxical reactions such as inflammation, and cause neoplasia. Human T-cell leukemia virus type 1 (HTLV-1) is an infectious agent that induces inflammation and neoplastic infiltration in the eye. To date, numerous HTLV-1 carriers have been treated with adalimumab to suppress inflammation out of necessity, when standard anti-inflammatory drugs such as steroids and immunosuppressive agents have proven inadequate to control the inflammation. Here, we clarify the safety of adalimumab for the eye under HTLV-1 infectious conditions in vitro. We used the adult retinal pigment epithelial cell line (ARPE)-19 cell line as ocular resident cells, and used MT2 and TL-Om1 as HTLV-1-infected cells. ARPE-19 and MT2/TL-Om1 were co-cultured, and then adalimumab was administered. Production of cytokines and chemokines, TNF-α receptor (TNF-R), HTLV-1 proviral load (PVL), and apoptosis were measured to assess the effects of adalimumab. Contact between ARPE-19 and MT2/TL-Om1 produced inflammatory cytokines such as TNF, interleukin (IL)-6, IL-8 and IL-10, and transduced chemokines such as interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), monokine induced by interferon-γ (MIG), and regulated on activation, normal T cell expressed and secreted (RANTES). No inflammatory cytokines and chemokines were exacerbated by adalimumab. Expression of TNF-R on ARPE-19 and MT2/TL-Om1 cells, HTLV-1 PVLs of MT2/TL-Om1 cells, and cell growth rate and apoptotic rate of ARPE-19 were unaffected by adalimumab. In conclusion, adalimumab does not appear to exacerbate HTLV-1-associated inflammatory conditions in the eye or increase PVL in HTLV-1-infected T cells. These data suggest that adalimumab could be used safely for the eye under HTLV-1 infectious conditions from the perspective of in vitro assessment.
Highlights
Levels of cytokines (IL-6, IL-8, IL-1β, IL-12p70, IL-10, and tumor necrosis factor (TNF)) and chemokines (RANTES, MIG, monocyte chemotactic protein-1 (MCP-1), and inducible protein-10 (IP-10)) secreted by each of adult retinal pigment epithelial cell line (ARPE)-19, MT2, Jurkat, ARPE-19 co-cultured with MT2/TL-Om1, and ARPE-19 co-cultured with Jurkat were measured (Figure 1)
IL-6, IL-10, and TNF were produced in ARPE-19 co-cultured with MT2, but not in ARPE-19 alone or in co-culture with TL-Om1 and Jurkat
Levels of TNF and IL-10 appeared similar in ARPE-19 co-cultured with MT2
Summary
Tumor necrosis factor (TNF)-α antibody was introduced in the late 1990s as a molecularly targeted agent and has since seen wide use against a variety of inflammatory diseases, including rheumatoid arthritis (RA; Bathon et al, 2000), psoriasis (Leonardi et al, 2003), ankylosing spondylitis (Braun et al, 2005), ulcerative colitis (Rutgeerts et al, 2005), and inflammatory bowel disease (Rutgeerts et al, 2004). Adalimumab (ADA), a fully human monoclonal TNF-α antibody, is most widely used as a biologic therapy for a variety of inflammatory diseases (Mullard, 2018). Infection by HTLV-1 causes various human diseases, representing hematological neoplasms such as adult T-cell leukemia/lymphoma (ATL; Uchiyama et al, 1977), and inflammatory diseases such as HTLV-1-associated myelopathy (HAM; Osame et al, 1986) and HTLV-1 uveitis (HU; Mochizuki et al, 1992; Kamoi, 2020)
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