Infiltration of the synovium by mononuclear cells, namely lymphocytes and monocytes, is one of the main features of rheumatoid arthritis (RA) and is considered to be responsible for the development of the disease. In this study in 31 consecutive patients with RA, we investigated whether peripheral blood monocytes exhibited markers of cellular activation related to cell migration. Using flow cytometry with the respective specific antibodies, we studied the expression of integrins CD11a, CD11b, CD11c, CD49d (VLA‐4), and CD49e (VLA‐5) on monocytes from patients with RA and from normal (N) subjects. IL‐1β, IL‐6, and tumour necrosis factor‐alpha (TNF‐α) production by cultured monocytes was measured by immunoassay. Adhesiveness of monocytes was studied on various surfaces (plastic, human fibronectin, gelatin‐coated plasma, subendothelial matrix) and on cultured endothelial cells under basal conditions or after stimulation by IL‐1β. An increased number of CD14+ monocytes (Mo) from RA patients expressed the CD11b molecule (RA Mo = 90.3%, N Mo = 83.4%, P < 0.005). The expression of CD11b on CD14+ monocytes was significantly increased in RA patients (median fluorescence intensity (FI): RA Mo = 145 (range 80–466) units; normal Mo = 95 (range 24–164) units; P < 0.003). Production of extracellular IL‐1β and IL‐6 by RA monocytes was significantly enhanced compared with monocytes from normal subjects (IL‐1β : RA = 2.65 ± 0.91 ng/ml versusN = 1.35 ± 0.85 pg/ml, P < 0.05; IL‐6: RA = 4.83 ± 0.90 ng/ml versusN = 2.40 ± 0.95 ng/ml, P < 0.05). Compared with normal monocytes, RA monocytes exhibited increased adhesion to the various surfaces studied (plastic, P < 0.01; fibronectin, P < 0.01; and gelatin‐coated normal or RA plasma, P < 0.01) as well as to unstimulated (P < 0.01) and IL‐1β‐stimulated endothelial cells (IL‐1β for 4 h, P < 0.05; IL‐1β for 24 h, P < 0.05). In our study, blood monocytes from RA patients exhibited features of activation related to cell adhesion.

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Oromucosal administration of [125I]-labeled recombinant human interferon-alpha1-8 (IFN-alpha1-8), which is biologically active in the mouse, resulted in readily detectable levels of radioactivity in the serum of animals within 5 min. Biologically active IFN could not be detected in the serum at any time after oromucosal administration, however, and SDS-PAGE analysis showed that the material present in the serum was of low molecular weight and most probably reflected absorption of degradation products following digestion of IFN in the stomach and small intestine. Furthermore, oromucosal administration of murine IFN-alpha/beta (MuIFN-alpha/beta) had no significant effect on the expression of IFN-responsive genes in either peripheral blood mononuclear cells or splenic lymphocytes even though in the same animals IFN treatment activated gene transcription locally in the lymphoid tissue of the oropharyngeal cavity and caused a marked systemic antiviral activity. Oromucosal administration of MuIFN-alpha/beta had no significant effect on either the number of circulating peripheral blood leukocytes or the number of granulocyte-macrophage colonies recovered from the bone marrow of IFN-treated animals. These results suggest that the mechanism of action of oromucosal IFN therapy is distinct from that of parenterally administered IFN and may involve, in the abundant lymphoid or epithelial tissue of the oropharyngeal cavity, either production of a soluble factor or activation of a specific cell population that enters the circulation to mediate the elimination of virus-infected or neoplastic cells.

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