Production of the neutrophil-activating peptide (NAP)-l/IL-8 by mononuclear phagocytes from patients with RA and from control subjects was studied under various conditions. Mononuclear cells from bone marrow (BMMC), PBMC, and synovial fluid (SFMC) were cultured for up to 48 h in the absence or presence of Escherichia coli LPS, different interleukins, interferon-gamma, zymosan, or immune complexes, and the neutrophil-stimulating activity released into the culture medium was determined. As shown by neutralization with an antiserum raised against human recombinant NAP-1/IL-8, over 90% of this activity could be attributed to NAP-1/IL-S.In unstimulated mononuclear cells from control individuals and BMMC from RA patients, the production of NAP-l/IL-8 was very low and was enhanced moderately by stimulation with LPS. By contrast, the spontaneous production of NAP-1/IL-S was 3-to 10-fold higher in PBMC and even much higher in

Objective. To evaluate the influence of food on the bioavailability of an oral dose of methotrexate in patients with rheumatoid arthritis.Methods. Methotrexate (15 mg) was given intravenously and orally, with or without a meal, to 10 patients. Blood samples were drawn at specific intervals to evaluate drug levels.Results. Food reduced the peak concentration, from a mean of 0.71 pmoleshiter to 0.49 pmoles/liter (P < 0.02), and slightly increased the time to peak concentration, from a mean of 1.3 hours to 2.0 hours. Bioavailability was highly variable (range 28-9470) but was not affected by food intake. Conclusion. Bioavailability of oral methotrexate shows marked interindividual variation but is not affected by the presence of food.Methotrexate, a potent inhibitor of dihydrofolate reductase, was introduced into human pharmacology as an antineoplastic agent. It is increasingly being employed at low doses (5-25 mg weekly) as a secondline drug for rheumatoid arthritis that has been refractory to corticosteroid therapy (1) the high doses typically given to combat malignant diseases (2). Relatively little is known about the pharmacokinetics of low doses of this agent (3-5). Oral doses of less than 30 mg/m2 of body surface have been shown to be well absorbed (2), but milk is known to affect the methotrexate absorption in children with leukemia (6).Only one published study has addressed the bioavailability of methotrexate in patients with rheumatoid arthritis (4). In that study, the bioavailability of an oral dose of methotrexate was highly variable, ranging from 4% to 191%. Whether food affects the bioavailability of low-dose methotrexate is unknown. Although oral administration of methotrexate could be desirable for patients with rheumatoid arthritis, therapeutic success depends on adequate absorption. We therefore studied the bioavailability of methotrexate, and whether it was influenced by food, in patients with rheumatoid arthritis. PATIENTS AND METHODSPatient population. The bioavailability of methotrexate was studied in 10 patients (5 men and 5 women) with classic rheumatoid arthritis (7). The patients had a mean 2 SD body weight of 69 1-11 kg (range 56-90) and were 58 5 8 (mean 2 SD) years old (range 45-66). Eight patients were taking nonsteroidal antiinflammatory agents, and 5 were taking prednisone. All medications were withheld the day of the study. No other concomitant drugs, in particular, no drugs known t o induce or inhibit the microsomal oxygenase system, were taken.All patients had normal renal and hepatic function, as determined by assessing plasma levels of creatinine, liver function tests, and galactose elimination capacity. Four patients had been taking methotrexate for more than 1 year and 4 for less than 2 weeks. The study was approved by the

SUMMARYWe describe a 33-yr-old man suffering from severe vertebral osteoporosis and urticaria pigmentosa due to systemic mast cell disease (SMCD). Because i.v. clodronate therapy could not prevent further vertebral fractures, an additional treatment with interferon alpha-2b was initiated. During 24 months of treatment, our patient had no further pain episodes, no new vertebral fractures were discovered, trabecular bone mineral density (BMD) increased significantly and urticarial symptoms improved. Nevertheless, the extent of skin lesions remained unchanged. On histological examination, a remarkable decrease of mast cells was observed in the bone marrow, but not in the skin. Five months after discontinuation of interferon alpha-2b, trabecular BMD decreased and urticarial symptoms deteriorated. These findings illustrate a beneficial effect of interferon alpha-2b on SMCD-induced osteoporosis as well as urticarial symptoms, and raise the question whether this treatment may have a diverse impact on mast cell populations in different tissues.

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