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Objectives-To determine whether fibroblasts from patients with systemic sclerosis (SSc) produce excessive amounts of endothelin-1 (ET-1), which is recognised as having vasoconstrictive properties and as having a potent mitogenic effect on fibroblasts Methods-Dermal fibroblasts were removed from 11 patients with SSc and from five normal controls (NC). The assay of ET-l protein was measured by an ELISA that used two anti-ET-1 antibodies. The gene expression of prepro ET-1 mRNA was evaluated by a reverse-transcriptase polymerase chain reaction (RT-PCR) method. Results-Levels of ET-1 protein were significantly higher in SSc fibroblast cultures than in those of normal fibroblasts (p < 0.01). The expression of prepro ET-1 mRNA was also higher in SSc fibroblasts than in normal fibroblasts. The addition of interleukin-lB (IL-1>) increased the production of ET-1 by fibroblasts. Conclusion-The findings indicate that the overproduction of ET-1 is a novel abnormal function in SSc fibroblasts, and that ET-1 induced by fibroblasts may play a role in the fibrosis and Raynaud's phenomenon of SSc.

SUMMARY Introducing avidin‐biotin complex ELISA for anti‐DNA antibody, the mechanism of in vitro production of anti‐ssDNA antibody as well as of polyclonal immunoglobulin mediated by an IL‐6‐IL‐6R loop was studied in patients with systemic lupus crythematosus (SLE). Regardless of the presence or absence of T cells, B cells from SLE patients could produce IgG anti‐ssDN A antibody as well as total IgG without any stimulation. Low density B cells obtained by Percoll gradient density cenlrifugation responded to rIL‐6 to produce IgG and IgG anti‐ssDNA antibody. rIL‐2 and rIL‐4 had lesser effects on the differentiation of low density B cells. In fact, IL‐6R was preferentially expressed on low density B cells from active SLE patients, as detected by anti‐IL‐6R MoAb, MT18, which did not inhibit IL‐6 binding. SLE B cells, especially high density B cells, produced greater amounts of IL‐6 in culture supernatants than did T cells, regardless of whether disease was active or inactive. Normal T cells and B cells did not produce significant amounts of IL‐6. Thus, endogenous IL‐6 produced by high density B cells bound to the IL‐6R preferentially expressed on the low density B cells, and drove them into terminal differentiation, especially in active SLE patients. Further, addition of polyclonal anti‐IL‐6 or anti‐IL‐6R MoAb (PM1). which inhibited IL‐6 binding, both inhibited IgG anti‐ssDNA antibody as well as total IgG production by SLE B cells in a dose‐dependent manner. These results suggest that interruption of the autocrine IL‐6 loop would be of therapeutic value in SLE.

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The complete nucleotide sequence of the gene for a cell surface protein antigen (SpaA) of Streptococcus sobrinus MT3791 (serotype g) was determined. The spaA gene consisted of 4,698 bp and coded for a protein of 170,202 Da. A putative signal peptide was found in the amino-terminal end of the protein. A potential promoter sequence and a putative Shine-Dalgarno sequence preceded the open reading frame. Two internal repeating amino acid sequences were present in SpaA. One repeating region, located in the amino-terminal region, was rich in alanine, and the other, located in the central region, was rich in proline. The molecular structure of SpaA was very similar to that of the surface protein antigen of Streptococcus mutans.