tion, the ratio of arachidonic acid to eicosapentaenoic acid in the patients' neutrophil cellular lipids decreased from 81:l to 2.7:1, and the mean generation of leukotriene B4 (with calcium ionophore stimulation) significantly declined by 33%. The mean neutrophil chemotaxis to both leukotriene B4 and FMLP significantly increased toward the normal range at week 6. The generation of 5-lipoxygenase products by calcium ionophorstimulated monocytes was not significantly suppressed, but a significant decline (37 %) in plateletactivating factor generation was noted at week 6. The modulation of these measures of leukocyte inflammatory potential suggests that fish oil supplementation may have an antiinflammatory effect.Dietary supplementation with fish oil fatty acids, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) in healthy volunteers has been shown to increase the relative content of EPA in leukocyte membranes and to decrease the response of the leukocytes to both transmembrane and calcium ionophore activation (1). The chemotactic dosedependent response of neutrophils to leukotriene B4 (LTB4) was significantly suppressed at 6 weeks of supplementation, and the chemotactic sensitivity was restored when the supplement was discontinued. The 5-lipoxygenation of arachidonic acid in response to activation with calcium ionophore was inhibited at 2 points. Fatty acid hydrolase function was attenuated, as defined by a reduced release of labeled arachidonic acid from prelabeled neutrophils and monocytes. Function of the 5-lipoxygenase enzyme (Figure 1) was suppressed, as determined by reduced generation of the sequential arachidonic acid-derived reaction products, 5-hydroperoxyeicosatetraenoic acid (measured

To evaluate the association of alleles of regions having regulatory potential in the IL-6 gene, with SLE, the AT-rich minisatellite in the 3Ј flanking region and the 5Ј promoter-enhancer of the IL-6 gene were genotyped by PCR-and RFLPbased methods. The AT-rich minisatellite allele distribution pattern was significantly different in SLE (n = 146) as compared to 139 controls ( 2 7 = 48.97, P = 0.001, Caucasians; and 2 7 =19.93, P = 0.006, African-Americans). In either race, short allele sizes (р792 bp) were seen exclusively in SLE patients (P = 0.001), whereas the 828-bp allele was overrepresented in controls (P = 0.015 and 0.002). In contrast, there was no preferential association of SLE with G/C alleles in the 5Ј region of the IL-6 gene. Furthermore, our results suggest that the 3Ј minisatellite alleles have biological significance: (1) B lymphoblastoid cells of patients having one or two SLE-associated alleles secreted IL-6 in 3-to 4-fold higher levels than non-allelic cells (P Ͻ 0.05); (2) higher percentages (approximately 4-fold) of IL-6 positive monocytes were observed in individuals having SLE-associated IL-6 alleles; (3) in lupus patients having SLE-associated minisatellite alleles, IL-6 mRNA stability was significantly enhanced.

Ten patients with rheumatoid arthritis were entered into a 24-week pilot study of oral cyclosporin A at a starting dosage of 6 mg/kg/day, followed by a 12-week washout period. Significant improvement in clinical parameters was observed at 12 weeks and 24 weeks (P < 0.02 versus baseline for joint pain and joint swelling indexes and patient and physician assessments; P < 0.04 versus baseline in the numbers of painful/ tender joints and swollen joints). Adverse reactions were varied: renal impairment occurred in all patients and hypertension occurred in 7. All patients demonstrated an increase in defined disease activity at cessation of treatment and through the washout period. Cyclosporin A is clinically effective in the treatment of patients with refractory rheumatoid arthritis, but its value as an intervention therapy is limited by its toxicity.Patients with rheumatoid arthritis (RA) are generally treated with antiinflammatory drugs and with possible disease-modifying agents such as gold salts, hydroxychloroquine, or penicillamine (1-3). When this approach has been unsuccessful, either because of