SUMMARYThe effect of fibronectin on IL-1a, IL-1j3, tumour necrosis factor-alpha (TNF-a), and IL-6 production was investigated with cultured monocytes isolated from human peripheral blood. Monokine concentrations were determined by both ELISA and bioassay. Fibronectin markedly stimulated the secretion of IL-1 a, IL-1,6, TNF-a and IL-6 from cultured monocytes in a dosedependent manner, with the maximal effect apparent within 24 h. Northern blot analysis revealed a marked increase in the abundance ofmRNA specific for each monokine on exposure ofmonocytes to fibronectin. Monoclonal antibodies to the a chain of very late antigen (VLA)-5, the,61 integrin, the a chain of Mac-I, and the ,62 integrin, as well as the synthetic peptide of GRGDSP (which corresponds to the cell-binding domain of fibronectin), inhibited (>50%) fibronectin-induced monokine production. Monoclonal antibodies to the a chain ofVLA-4, and the a chain of LFA-I, as well as the synthetic peptide CS-I (which corresponds to the alternatively spliced connecting segment of fibronectin) and the control peptide GRADSP, had no inhibitory effect on monokine production. A MoAb, R60, that recognizes an epitope of the fibronectin molecule that includes the RGD sequence, inhibited monokine production, whereas the MoAb Y16, which recognizes another epitope of fibronectin not including RGD, did not. These results indicate that fibronectin-induced production of IL-Ia, IL-1,6, TNF-a and IL-6 from cultured monocytes is mediated predominantly by interaction of the cell-binding domain of fibronectin with VLA-5, although Mac-1 also may contribute to this effect of fibronectin. Our results indicate that the interaction of fibronectin with integrins may contribute to the cytokine network in inflammatory response.

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SUMMARYWe examined ihc TNF-x activity in culture supernalants of monocytes isolated from the peripheral blood of patients with SLE and of normal individuals. The monocytes from patients wilh SLE stimtilated with silica particles, lipopolysaccharide or Staphylococcus aureus Cowan I secreted significantly lower amounts of TNF-a: than did normal monocytes, A decreased TNF mRNA expression was observed in peripheral blood mononuclear cells stimulated by tnitogens from patients with SLE. Furthermore, we examined the effect of recombinant TNP-5 (rTNF-:() on the B cell function in SLE patients. rTNF-a inhibited the spontaneous Bcell proliferation of SLE. but tended to enhance the normal B cell proliferation. Spontaneous IgM production from SLE B cells was inhibiled by rTNF-a. but that from normal B cells was not. Spontaneous IgG production was unaffecled by rTNF-a. Also. rTNF-x did not affect the viability of B cells. These findings suggest that an Impaired TNF-a production and an abnormal B cell response to TNF-a play a role in the immunological dysfunction in patients with SLE.

We estimated the concentration of soluble IL-2R (sIL-2R) in the serum of patients with systemic lupus erythematosus (SLE) and examined the relationship between the serum levels of sIL-2R and clinical features or laboratory data. We found that elevated levels of sIL-2R were present in the serum of SLE patients with discoid rash, and sIL-2R concentrations were correlated with the soluble CD4 and soluble CD8 concentrations but not with classical serological marker, anti-DNA antibody or complement titer.

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