Enhanced Production Of Interleukin‐1 And Tumor Necrosis Factor α By Cultured Peripheral Blood Monocytes From Patients With Scleroderma

Abstract

Cultured peripheral blood mononuclear cells from 20 patients with scleroderma were shown to produce high levels of interleukin-la, interleukin-lp, and tumor necrosis factor a. There were positive correlations between the production of these 3 molecules. Purified monocytes from these patients produced much more tumor necrosis factor a than did those from normal subjects, even without lipopolysaccharide stimulation. These results show the hyperactivity of monocytes from scleroderma patients.Diffuse or perivascular cellular infiltration is often observed in either the dermis or the subcutaneous tissues of patients with scleroderma (systemic sclerosis; SSc). These infiltrates have been shown to predominantly consist of either T lymphocytes or both

Estudo da densidade óssea na esclerodermia sistêmica

“…Esses dados sugerem que a osteopenia em mãos, na esclerodermia sistêmica, está associada mais a fenô-menos regionais, tais como tendência à imobilidade causada pela fibrose dérmica, isquemia crônica decorrente da endarterite obstrutiva da microcirculação e reabsortiva local [35][36][37] do que a qualquer alteração sistêmica propriamente dita.…”

“…Além disso, a síntese de TGF-β é fortemente estimulada pelo fator de crescimento derivado de plaquetas (PDGF), que se encontra elevado no soro de pacientes com esclerodermia 43 . Por outro lado, certas citocinas, como a interleucina 1 (IL-1) e o fator de necrose tumoral alfa (TNF-α), que aumentam a reabsorção óssea, são encontradas nos locais de maior atividade da doença 37,39 , o que justificaria o encontro radiológico de osteopenia e osteólise regionais (mãos, pés, ramo da mandíbula, costelas, etc.). Entretanto, as citocinas mencionadas não teriam ação sistêmica em nível ósseo, visto que os níveis séricos estão normais em pacientes com esclerodermia sistêmica 39 .…”

Enhanced production of transforming growth factor-beta (TGF-β) during autologous mixed lymphocyte reaction of systemic sclerosis patients

“…Fither IL-1 or concanavalin A (Con A) was reported to induce active TGF-/3 from purified T cells without the proliferative response, although a coexistence of both stimulations did not induce it [22]. The enhanced production of TGF-/J from MNC of SSc might come from inadequate T cell stimulation during AMLR, because SSc monocytes were shown to produce higher levels of IL-1 [7].…”

“…Among them, cytokines such as IL-1 and tumour necrosis factor-alpha (TNF-tt) which induce the proliferation of fibroblasts and/or the synthesis of collagens have been suggested to play a key role in the fibrotic mechanism of SSc. We previously reported the hyperproduction of IL-1 and TNF-ci by monocytes of SSc patients [7]. Recently, TGF-/3 has been shown to induce fibroblasts to increase extracellular matrix production (8,9], and is also thought to be deeply involved in ihe fibrosis of SSc.…”

Antibodies to membranes of endothelial cells and fibroblasts in scleroderma

“…The clinical association or 'overlap' of scleroderma with other autoimmune connective tissue diseases such as systemic lupus erythematosus and polymyositis [1], together with its high incidence of distinctive autoantibodies [2,3], circulating immune complexes [4,5] and evidence of T cell activation [6] with elevated levels of cytokines [7,8], all strongly suggest that autoimmune mechanisms are involved in the pathogenesis of the disease. The development of scleroderma-like lesions as a feature of chronic graft-versus-host disease, both experimentally [9] and in man [10], further supports this concept.…”