SUMMARYThe characterization of a salivary factor cross-reacting with IL-1 receptor antagonist (IL-1Ra) is described. The apparent molecular weights of two species were 23 kD, consistent with the secreted peptide (sIL-1Ra), and 20 kD, consistent with the intracellular peptide (icIL-1Ra). It had an inhibitory activity on IL-1-stimulated fibroblasts, which is characteristic of IL-1Ra. Its source was the oral mucosa and not the salivary glands. Saliva from patients with SS contained significantly less IL-1Ra than saliva from controls. The decrease was marked in patients with early dental loss but whose xerostomia was still partial. In SS, the salivary IL-1/IL-1Ra imbalance may promote inflammatory lesions in the mouth and impede mucosal cell differentiation.

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SUMMARYRegulatory cytokines mediate the participation of oral mucosal epithelial cells (OMEC) in local immune responses. The aim of this study was to characterize the isoforms of IL-1 receptor antagonist (IL-1ra) in cultured human primary OMECs and to compare its production with that of IL-1 alpha (IL-1a ) and IL-1 beta . Western blot analysis showed that IL-1ra was 22 kDa in size hence slightly smaller than monocyte IL-1ra (25 kDa). A minor form of 20 kDa was also found in unstimulated cell culture lysates. In culture supernatants, IL-1 bioactivity increased after IL-1ra neutralization, indicating that the baseline production of IL-1ra is biologically relevant. Immunohistochemistry showed a relation between IL-1ra and involucrin expressions, suggesting that intracytoplasmic IL-1ra may be involved in cell terminal differentiation. In unstimulated culture lysates, there was far more IL-1ra than IL-1a and IL-1b . TGFb1 markedly increased the IL-1ra/IL-1b ratio from 93´6 : 1 to 300 : 1. IL-4, which is generally described as an anti-inflammatory cytokine, increased IL-1 but not IL-1ra production. TNF-a increased intracellular production of the three IL-1 members. IL-1ra levels were lower in supernatants than in lysates of cultured cells. Our results show that human OMECs constitutively produce significant amounts of a biologically active form of IL-1ra. TGF-b 1 mp-regulation points to a positive amplification loop and IL-4 to a down-regulation loop, both including Th2 cells and OMECs. They may be important in oral tolerance and IgA production, respectively.

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