Tenidap, but not Nonsteroidal Anti‐Inflammatory Drugs, Inhibits T‐Cell Proliferation and Cytokine Induction

Abstract

T-lymphocytes are involved in the inflammatory response that occurs in affected joints of patients with rheumatoid arthritis (RA). Some second-line disease modifying anti-rheumatic drugs used in the treatment of patients with RA are known to block T-cell activation. The present study assessed whether tenidap, an investigational anti-rheumatic drug, affects in vitro T-cell responses such as proliferation and cytokine production. It was found that tenidap, in contrast to several nonsteroidal anti-inflammatory drugs, inhibits anti-CD3 or IL-2 driven proliferative responses of cloned human T-cells. Furthermore, tenidap was found to inhibit IFN-gamma production as well as the induction of mRNA encoding IFN-gamma or TNF-alpha. The results indicate that tenidap may exert at least part of its anti-inflammatory activity via inhibition of T-cell function and cytokine production.

A comparison of the disease-modifying and cytokine-regulating activities of tenidap, piroxicam and cyclosporin-A using the adjuvant-induced model of arthritis in rats

“…It is suggested that prevention of arthritis by CsA and lobenzarit may be due to suppression of key cytokines (IFN-7, TNF and IL-2) during the early stages of disease development [6]. The ability of tenidap to inhibit these T cell cytokines in vivo is consistent with recent reports showing that tenidap inhibits T cell proliferation and cytokine production in vitro [21]. However, complete disease prevention was only noted when tenidap was administered with the adjuvant in this study.…”

“…These drugs appear to be effective by suppressing release of interferon-~/(IFN-~'), interleukin-2 (IL-2) and possibly tumour necrosis factor (TNF) from lymph node cells during the initiation of the disease. Recent reports have shown that a new antirheumatic drug, tenidap, also regulates the production of these cytokines in vitro [7,8].…”

Comparison of the Immunosuppressive Effects of Dexamethasone, Flunixin Meglumine and Meloxicam on the In Vitro Response of Calf Peripheral Blood Mononuclear Cells

“…However, we found that both FLU and MEL inhibited lymphocyte proliferation in a dose-dependent manner in vitro. In humans, COX-2-specific inhibitors such as NS398 (3.1-31 μg/ml) or celecoxib (3.8-38 μg/ml) severely diminished T-cell activation, including IL-2, TNF-α and IFN-γ production, and cell proliferation [9], while the nonselective NSAID tenidap inhibited the production and mRNA expression of IL-2 and IFN-γ in T lymphocytes [7].…”

Effects of flunixin meglumine and ketoprofen on mediator production inex vivoandin vitromodels of inflammation in healthy dairy cows

“…In humans, some COX‐2 selective NSAIDs inhibited the production of IFN‐γ and TNF‐α, while nonselective NSAIDs inhibited production of IFN‐γ, but not interleukins expression (Dolhain et al. , 1995; Iñiguez et al.…”

“…In humans, some COX-2 selective NSAIDs inhibited the production of IFN-c and TNF-a, while nonselective NSAIDs inhibited production of IFN-c, but not interleukins expression (Dolhain et al, 1995;Iñ iguez et al, 1999). In a study about calves, the authors found that FM and some NSAIDs inhibited lymphocytes proliferation in a dose-dependent manner in vitro and tended to decrease the expression of IFN-c, but not interleukins (Maeda et al, 2005).…”