Tumor necrosis factor alpha inhibitors have no effect on a human T-lymphotropic virus type-I (HTLV-I)-infected cell line from patients with HTLV-I-associated myelopathy

Shoichi Fukui,Akihiko Okayama,Tatsufumi Nakamura,Hideki Nakamura,Yoshiko Takahashi,Katsunori Yanagihara,Hiroo Hasegawa,Atsushi Kawakami,Naoki Iwamoto

doi:10.1186/s12865-017-0191-2

Abstract

BackgroundWhile tumor necrosis factor alpha (TNF-α) inhibitors (TNFi) and other biologics are very effective against autoimmune diseases, they can also cause infectious diseases. Therefore, it is important to clarify whether the TNFi sometimes used to treat patients with rheumatoid arthritis (RA) complicated with human T-lymphotropic virus type-I (HTLV-I) infection have the unintended side effect of promoting HTLV-I proliferation.MethodsWe used the HTLV-I-infected cell line HCT-5, derived from spinal fluid cells of a patient with HTLV-I associated myelopathy, to evaluate the production of cytokines and chemokines, TNF-α receptor (TNFR), the expression of HTLV-I associated genes, the HTLV-I proviral load (PVL), the expression of HTLV-I structural protein, and apoptosis. We used Jurkat cells as a control.ResultsSupernatants of HCT-5 showed time-dependent elevations of IL-6, RANTES and ICAM-1. HCT-5 supernatants treated with infliximab, adalimumab, etanercept (ETN), golimumab and certolizumab pegol showed no significant differences in the levels of these molecules compared to the control. Neither TNFR1 nor TNFR2 expression was altered by any TNFi treatment, relative to phosphate-buffered saline (PBS) treatment, with the exception that TNFR2 was significantly decreased and internalized in HCT-5 cells by ETN treatment. The HTLV-I associated genes Tax and HBZ and the PVL levels were not significantly changed. Immunofluorescence staining of HCT-5 for an HTLV-I-associated protein, GAG, was also not significantly different between any of the TNFi treatments and the PBS treatment. DNA ladders as an index of apoptosis were not detected. Apoptotic cells were not increased by the addition of any TNFi.ConclusionsIn vitro, TNFi did not affect the cytokine profiles, expression of associated genes and proteins, proviral load or apoptosis of HCT-5 cells. The results suggested that TNFi treatment of RA patients complicated with HTLV-I might have no effect on HTLV-I infection.

Highlights

While tumor necrosis factor alpha (TNF-α) inhibitors (TNFi) and other biologics are very effective against autoimmune diseases, they can cause infectious diseases
In the Jurkat cells, there were no increases in these cytokines or chemokines, and most of the cytokines and chemokines were below measurable limits
Forty-eight hours after the THP-1 cells were stimulated by LPS (1 μg/mL) with each Tumor necrosis factor alpha inhibitor (TNFi), we measured the levels of IL-6, TNF-α, ICAM-1 and RANTES in the culture supernatants by enzyme-linked immunosorbent assays (ELISAs)

Summary

Introduction

While tumor necrosis factor alpha (TNF-α) inhibitors (TNFi) and other biologics are very effective against autoimmune diseases, they can cause infectious diseases. It is important to clarify whether the TNFi sometimes used to treat patients with rheumatoid arthritis (RA) complicated with human T-lymphotropic virus type-I (HTLV-I) infection have the unintended side effect of promoting HTLV-I proliferation. Human T-lymphotropic virus type-I (HTLV-I) is a retrovirus that infects 10 to 20 million people worldwide [1]. The majority of infected people remain asymptomatic, HTLV-I is associated with severe diseases such as adult T-cell leukemia/lymphoma (ATL) and HTLV-I-associated myelopathy (HAM). Tumor necrosis factor alpha (TNF-α) inhibitors (TNFi) are an important agent for a number of inflammatory conditions, including rheumatoid arthritis (RA), [4] ankylosing spondylitis, [5] and inflammatory bowel disease [6]. With respect to viral infection, hepatitis B virus (HBV) occasionally reactivates, and a flare of HBV disease may occur [7]

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