Low levels of interleukin‐4 and high levels of transforming growth factor β in rheumatoid synovitis

Abstract

Since interleukin-4 (IL-4) displays agonistic effects on both T and B cells, we studied whether this lymphokine is involved in rheumatoid synovitis, a disease characterized by intense T cell infiltration and B cell stimulation. Rheumatoid arthritis synovial fluids (RA SF) contained no (<15 pg/ml) or very low amounts (C25 pg/ml) of IL-4, as measured by a sensitive and specific enzyme-linked immunosorbent assay. No IL-4 was produced by unstimulated rheumatoid synovial membrane. RA SF were found to inhibit phorbol myristate acetate (PMAWependent proliferation of normal peripheral blood lymphocytes (PBL). An inhibitory fraction with an apparent molecular weight of 150 kd was isolated by gel filtration. The inhibitory fraction strongly blocked the proliferation of PBL induced by PMA, PMA + IL-2, or PMA + IL-4. However, this fraction was less effective in blocking the proliferation of PBL induced by PMA + IL-2 + IL-4. High levels of transforming growth factor p (TGFP) were found in these RA SF, and an anti-TGFP antibody was able to Interleukin-4 (IL-4), a T cell-derived lymphokine first described in terms of its ability to activate B cells, was later shown to act on T cells (6,7). Human IL-4 can induce the proliferation of activated T and B cells (%lo), the expression of the low-affinity receptor for IgE (Fc, R2) on B cells (1 l), the production of IgG and IgM by activated B cells (12). and the expression of CD8 on CD4+ T cell clones (13). Thus, the large number of activated T and B cells in rheumatoid synovitis (1-3). the presence of CD4+, CD8+ T cells (14). and the production of immunoglobulins by the synovium (2) led us to consider a role for IL-4 in rheumatoid synovitis.We studied synovial fluids (SF) from rheuma-

Enhanced and persistent levels of interleukin (IL)-17+CD4+ T cells and serum IL-17 in patients with early inflammatory arthritis

“…In addition, many women experience improvement of their arthritis during pregnancy (reviewed in [35]), and the switch towards a Th2 profile in pregnancy may be at least partially responsible [36]. Synovial fluid from patients with RA has shown either low or absent IL-4 [37], although Raza et al demonstrated a distinct cytokine profile in synovial fluid (SF) which included IL-4 [2]. In general, the chemokines and cytokines found to be elevated in our EIA cohort may represent an activated immune system, which continues during established RA, although there are likely to be treatment effects in patients with long-standing disease.…”

Anti-cyclic citrullinated peptide antibodies and IL-23p19 in psoriatic arthritis

“…One possibility would be that these anti-CCP-positive patients with psoriasis may have coexistent RA. Both psoriasis patients and RA patients are recognized to be Th1-associated diseases [28,29]. Furthermore, both diseases are sensitive to anti-tumor necrosis factor-alpha agents [30][31][32][33][34][35][36].…”

Circulating T helper and T regulatory subsets in untreated early rheumatoid arthritis and healthy control subjects

“…In the current paradigm, although both Th1 and Th17 cells are described as contributing to RA pathogenesis [2,12,14], the role of Th1 cells is becoming controversial. In addition, the presence of IFN-g has been detected rarely in the synovial fluid of patients with RA [15,16]. Nevertheless, in established RA, IFN-g producing T cell clones have been found in synovial fluid and peripheral blood; hence, they indicate a Th1 phenotype [17].…”