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immune system includes activation of T cells and recruitment Autoantibody Production
of inflammatory cells such as macrophages into the sites of Experimental reduction of TNF-α activity may lead to reduced control
inflammation. In the model of experimental autoimmune uveitis of autoantibody formation and increased risk of infection. Clinically,
(EAU), it has been demonstrated that TNF-α may play a key role in antinuclear autoantibodies are found in up to 75% of patients.
uveitis. In the model of endotoxin-induced uveitis (EIU) in rats, an Fortunately, this leads to clinical lupus erythematosus only in rare
early rise of TNF-α in the aqueous humour and serum is detectable. cases. Due to its chimaeric character, infliximab can also induce
Injection of TNF-α into the vitreous of rats
results in antichimaeric antibodies:
it can lead to anaphylactic reaction
formation of neutralising antibodies, as well as anti-DNA antibodies,
which is why it is normally administered with methotrexate (MTX). The
Tumour necrosis factor-α is a cytokine extent to which similar effects are seen with adalimumab is unclear
that is produced in a soluble and
at the moment.
membrane-bound form by different Infection
cells of the immune system, including
It seems that all TNF-α-blocking agents can induce infections. In
particular, they can reactivate tuberculosis, which may result
macrophages, T cells and natural in sepsis. Recently, uveitis due to tuberculosis under etanercept has
also been described.
Therefore, before using TNF-α blockers,
tuberculosis must be excluded.
acute uveitis with infiltration of polymorphonuclear granulocytes. In Induction and Reactivation of Uveitis
patients with chronic uveitis, TNF-α levels have been shown to be Reactivation is a particular problem with etanercept,
elevated in serum, but less so in the aqueous humour.
Mice that drug can probably also induce uveitis for the first time, as has been
are deficient in p55 TNFr and p75 TNFr have attenuated ocular shown in patients with HLA-B27-associated arthritis and JIA, and
inflammation compared with controls, using an immune complex also in those with rheumatoid arthritis, a disorder that is not
model for uveitis.
A TNF-α receptor–immunoglobulin G (IgG) fusion normally associated with uveitis. In some patients, a rechallenge
protein has been shown to decrease the intensity and prolong the has shown the definite role of etanercept in this process. Induction
onset of uveitis.
Therefore, there seems to be a clear rationale for of uveitis has only rarely been described with infliximab and
the use of TNF-α-blocking agents in uveitis. adalimumab. The anti-TNF-α antibodies bind the transmembrane-
bound TNF of T cells, inducing apoptosis of activated lymphocytes.
Available Tumour Necrosis Guignard et al.
suggest that this apoptosis effect, which is not
Factor-α-blocking Drugs found in etanercept, may be a reason for the different effects of
Currently, there are three TNF-α-blocking drugs in clinical use: the three drugs.
etanercept, infliximab and adalimumab. Etanercept (Enbrel
) is a
soluble fusion protein of the extracellular ligand-binding portion of Induction and Reactivation of Demyelinating Diseases
human TNF receptor p75 and the Fc portion of human IgG
. In There are multiple reports about induction of retrobulbar optic
particular, it inhibits the trimer form of TNF-α – inhibiting TNF-β to a neuropathy, optic neuritis and multiple sclerosis.
This seems to be
lesser extent – without affecting production or serum levels of TNF. It a side effect of this group of drugs, as suggested in case reports for
is injected subcutaneously at a dose of 0.8mg/kg once or twice a all three drugs.
week in children and adolescents. The half-life of etanercept is 4.25
days. Infliximab (Remicade
) is a chimaeric IgG
monoclonal antibody Tumour Necrosis Factor-α-blocking
composed of a human constant and a murine variable region. It Agents and Paediatric Uveitis
inhibits the monomer and trimer forms of TNF, blocking soluble and TNF-α blockers have become third-line drugs in the treatment of JIA-
transmembrane TNF-α. It is administered intravenously at a dose of associated uveitis, the only investigated form of paediatric uveitis.
3–10mg/kg over at least two hours every two to eight weeks. The However, recent reports and studies suggest that these three drugs
half-life of infliximab is eight to 9.5 days. Adalimumab (Humira
) is a have different effects in terms of managing the uveitic inflammation.
recombinant human IgG
human monoclonal antibody that binds
specifically to TNF-α, blocking soluble and transmembrane TNF-α. It Etanercept
is administered subcutaneously every other week at a dose of Smith et al.
showed in a very small randomised, placebo-
40mg/kg. As for infliximab, the half-life of adalimumab is eight to 9.5 controlled, double-masked study in children with mild uveitis that
days. All three drugs are approved for the treatment of various the effect of etanercept (seven patients treated) on anterior
rheumatic disorders in adults. Etanercept is also approved for the segment inflammation was not different from that of placebo (five
treatment of ankylosing spondylitis, psoriasis and JIA. The spectrum patients treated). Our group reported a retrospective study of 19
of side effects is becoming clearer after years of use. patients with uveitis
with JIA as underlying disease treated with
etanercept. There was mild improvement of the uveitis in seven
Side Effects patients and no response in nine patients, and three patients
Injection-site Reactions worsened. However, in all patients the arthritis responded well to
After injection of etanercept or adalimumab, reddening with treatment with etanercept.
In a prospective study with 10 patients
swelling at the injection site may occur. Although this is harmless, receiving etanercept and 10 receiving placebo, etanercept did not
it may lead to reduced compliance among patients. Cooling the skin show an effect in terms of preventing relapses of uveitis compared
before injection may help to control this side effect. with placebo.
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