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Although it is now accepted that killer-cell inhibitory receptors (KIRs), which were molecularly cloned in 1995, deliver negative signals to natural killer (NK) cells regarding the recognition of target cells, it is still unclear how the expression of these receptors on lymphocytes is regulated. Therefore, we investigated the regulation of expression of representative KIRs, CD158a and CD158b, by cytokines such as interleukin-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma). Neither IL-4 nor IFN-gamma affected the expression of CD158a/b, but incubation for 48 h with IL-2, which enhances the killer activity of NK cells, upregulated the expression of the KIRs. This upregulation by IL-2 was also observed in CD16-positive cells sorted from total lymphocytes. In contrast, IL-4, which is a down-regulator of IL-2-induced killer responses, did not change the level of CD158a/b expression when added after the IL-2 treatment. These findings suggest that IL-2 plays an important role in the regulation of CD158a/b expression, and might be involved in controlling NK activity via regulating expression of these molecules.

Anti-cyclic citrullinated peptide (CCP) antibody is a useful marker for the diagnosis and prognosis of rheumatoid arthritis (RA). Recently, clinical significance of follow-up in anti-CCP antibody titer has been pointed out. Thus, we investigated the serial determination in anti-CCP antibodies titer in RA patients. Six patients with RA, who were followed up for longer than 5 years, were assessed in anti-CCP antibodies and radiographs (Larsen score). Anti-CCP antibodies in frozen sera were measured using ELISA. As a result, 6 patients with RA were divided into two groups: one possessed high titers without variation, and the other was without high titers. Joint damage progressed during observation in 2 out of 3 patients with high anti-CCP titers in a retrospective assessment. In contrast, the RA patient, whose anti-CCP titer decreases although it had been high titer at baseline, did not show increase in the Larsen score. These findings suggest that it might be necessary to analyze changes in anti-CCP to predict the prognosis of joint destruction.

Crude preparations of Stephania tetrandra (ST), a traditional herbal medicine, have been used safely for arthritis and silicosis in China. The concentration of granulocyte elastase - alpha 1 protease inhibitor complex in plasma is enhanced in inflammatory processes, e.g. in septicaemia and rheumatoid arthritis (RA), being an expression of granulocyte activation during inflammatory response. It has previously been reported that ST showed beneficial and immunomodulatory effects in the treatment of relatively mild RA. After the administration of ST for 12 weeks, the proportion of granulocytes and the granulocyte count in peripheral blood decreased significantly. The lipid peroxide and human granulocyte elastase levels of stored plasma declined significantly. Furthermore, both the leukocyte/elastase ratio and granulocyte/elastase ratio increased significantly. The findings of this study suggest that the suppressive effect of ST administration on excessive granulocyte activation resulted in the improvement of inflammation with rheumatoid arthritis.

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