Neutralizing Inflammatory Cytokines in Nephritis

Wardle, E. N.

doi:10.1159/000188460

Cited by 5 publications

(2 citation statements)

References 27 publications

(29 reference statements)

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“…If these hypotheses are confirmed, then new therapies aimed at rapidly neutralizing proinflammatory cytokines, e.g. IL-1Ra and anti-TNF strategies [53,54], may attenuate glomerular damage and fibrotic sequelae, especially in severe forms of IgAN where natural mechanisms aimed at buffering the noxious effects of TNF and IL-1 may be deficient.…”

Section: Discussionmentioning

confidence: 99%

Imbalances in serum proinflammatory cytokines and their soluble receptors: a putative role in the progression of idiopathic IgA nephropathy (IgAN) and Henoch–Schönlein purpura nephritis, and a potential target of immunoglobulin therapy?

Rostoker

Rymer

Bagnard

et al. 1998

Clinical and Experimental Immunology

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Following recent experimental data suggesting an aggravating effect of circulating proinflammatory cytokines on the histological lesions of IgAN, we studied changes in serum proinflammatory cytokines and their soluble receptors and antagonists in patients treated with polyvalent immunoglobulins (15 with severe nephropathy who had indicators of poor prognosis: heavy proteinuria, hypertension, altered renal function and Lee's histological grade III or IV; and 14 with moderate forms of IgAN who had permanent albuminuria > 300 mg/day and < 2000 mg/day, Lee's histological grade II and a glomerular filtration rate > 70 ml/min) in comparison with healthy controls (n = 20) and patients with non-IgA nephritides (n = 50). These were measured by means of specific immunometric assays before and after 9 months of immunoglobulin therapy. Total tumour necrosis factor (TNF) serum and IL-6 levels were elevated in IgAN patients before therapy, relative to controls, and normalized after immunoglobulin therapy. Levels of soluble TNF receptor of type I (sR55) and type II (sR75) increased on immunoglobulin therapy. TNF index alpha-55,75 used to assess biologically available TNF-alpha (ratio of total TNF-alpha divided by levels of soluble TNF receptors sR55 and sR75) was elevated before therapy and was below healthy control values after 9 months of immunoglobulin administration. Levels of serum IL-1 receptor antagonist were low prior to immunoglobulin administration in patients with severe forms of IgAN, and normalized on therapy. Serum interferon-gamma was unmodified. The histological activity index correlated with serum total TNF-alpha, TNF index alpha-55,75 and serum IL-6 levels, whereas proteinuria correlated with serum total TNF-alpha and TNF index alpha-55,75 but not with serum IL-6. These data suggest that the overproduction of proinflammatory cytokine is unbalanced by their natural antagonists in IgAN and Henoch-Schönlein syndrome. This process may play a role in the progression of the disease and be one of the targets of immunoglobulin therapy.

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Section: Discussionmentioning

confidence: 99%

Imbalances in serum proinflammatory cytokines and their soluble receptors: a putative role in the progression of idiopathic IgA nephropathy (IgAN) and Henoch–Schönlein purpura nephritis, and a potential target of immunoglobulin therapy?

Rostoker

Rymer

Bagnard

et al. 1998

Clinical and Experimental Immunology

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“…It also became apparent that division of helper T lymphocytes into T‐helper 1 (Th1) and T‐helper 2 (Th2) varieties, as was described in mice in the 1980s, is applicable to man. Thus, in proliferative and progressive nephritides, in which a delayed hypersensitivity reaction accompanied by macrophages is taking place in the glomeruli 10 , the associated lymphocytes are of the Th1 type and they are producing interleukin (IL)‐2 and interferon (IFN)‐γ 11 . The reaction is the same as that used in the defense against bacteria, viruses and fungi, or intracellular parasites.…”

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confidence: 99%